Chromatin: Difference between revisions

Latest revision as of 21:53, 19 May 2026

The major structures in DNA compaction: DNA, the nucleosome, the 11 nm beads on a string chromatin fibre and the metaphase chromosome.

Chromatin is a complex of DNA and protein responsible for condensing and packaging chromosomal DNA. Chromatin is found in both bacterial^[1] and eukaryotic cells^[2]. This article deals almost exclusively with eukaryotic chromatin.

Eukaryotic chromatin consists primarily of DNA associated with histone proteins and numerous other chromatin-binding factors that contribute to genome organization and regulation. Chromatin packages long DNA molecules into compact structures while controlling access to genetic information for processes such as transcription, DNA replication, and DNA repair. During cell division, chromatin facilitates proper segregation of chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin.

Chromatin organization is often described at several structural levels. At the most basic level, DNA wrapped around histone octamers forms nucleosomes connected by stretches of linker DNA, producing a structure sometimes referred to as a “beads-on-a-string” fiber approximately 10–11 nm in diameter. Nucleosome arrays can interact with each other and with linker histones to form higher-order chromatin structures. 30-nm chromatin fiber has been observed in vitro, although its presence and prevalence in living cells remain debated^[3].

At larger genomic scales, chromatin is organized into loops and domains that contribute to the three-dimensional architecture of the genome. Chromosomes are further partitioned into compartments associated with active (euchromatin) or inactive (heterochromatin) chromatin states, and individual chromosomes occupy distinct spatial regions within the nucleus known as chromosome territories.

Many organisms exhibit variations in chromatin organization. For example, spermatozoa and avian red blood cells have more tightly packed chromatin than most eukaryotic cells. In contrast, some protozoa such as trypanosomatid do not DNA condense their chromatin into visible chromosomes at all.

Bacteria organize their DNA differently, forming a chromatin or nucleoid structure organized by nucleoid-associated proteins including H-NS and StpA^[4]. Some archaeal species encode histone proteins, and package DNA into nucleosome-like assemblies of variable size, sometimes referred to as hypernucleosomes.^[5]^[6]

Chromatin organization also varies throughout the cell cycle. During interphase, chromatin is generally less condensed, allowing access to RNA and DNA polymerases that transcribe and replicate the DNA. The local structure of chromatin during interphase depends on the specific genes present in the DNA.

During mitosis and meiosis, chromatin becomes highly compacted to facilitate the segregation of chromosomes. Within interphase nuclei, genomic regions differ in their degree of compaction and transcriptional activity. Actively transcribed regions are often associated with less condensed chromatin known as euchromatin, whereas transcriptionally inactive or repressed regions are frequently enriched in more compact heterochromatin.^[7] Chemical modifications of chromatin components, often so-called epigenetic modification, including histone tails methylation and acetylation also alters local chromatin structure and therefore gene expression.

Basic chromatin structure

Nucleosomes

The primary protein components of chromatin are histones. Nucleosome, the fundamental basic unit of chromatin, consists of DNA wrapped around a histone octamer containing two copies each of the core histones Histone H2A, Histone H2B, Histone H3, and Histone H4.^[3] Approximately 147 base pairs of DNA wrap around this histone octamer to form the nucleosome core particle.

File:Nucleosome 1KX5 2.png

A cartoon representation of the nucleosome structure. From PDB: 1KX5.

Neighboring nucleosomes are connected by stretches of linker DNA, which vary in length among organisms and cell types but typically range from about 20 to 60 base pairs. Arrays of nucleosomes connected by linker DNA form an extended fiber often described as a “beads-on-a-string” structure approximately 10–11 nm in diameter under low-salt or experimentally reconstituted conditions.

In addition to core histones, a linker histone H1 binds near the entry and exit sites of DNA on the nucleosome and contributes to higher-order chromatin organization. The nucleosome core particle, together with histone H1, is known as a chromatosome.

The nucleosomes bind DNA non-specifically, as required by their function in general DNA packaging. There are, however, large DNA sequence preferences that govern nucleosome positioning. This is due primarily to the varying physical properties of different DNA sequences: For instance, adenine (A), and thymine (T) is more favorably compressed into the inner minor grooves. This means nucleosomes can bind preferentially at one position approximately every 10 base pairs (the helical repeat of DNA)- where the DNA is rotated to maximize the number of A and T bases that will lie in the inner minor groove (see nucleic acid structure).

Historical 30-nm fiber model

File:30nm Chromatin Structures.png

"solenoid" structure and loose helix structure of historical 30 nm fiber

Under certain experimental conditions, nucleosome arrays can fold into more compact structures with diameters of approximately 30 nm. Early models proposed that chromatin fibers adopt regular helical arrangements, including a one-start solenoid model and a two-start zigzag model.

However, the existence of a uniform 30-nm chromatin fiber in living cells remains debated. Studies using cryo-electron microscopy^[8] and other high-resolution imaging methods have suggested that chromatin in many cell types forms irregular and dynamic nucleosome assemblies rather than regular 30-nm fibers^[3].

Three-dimensional genome organization

see Nuclear organization

File:Chromosome en.svg

the structure of chromatin within a chromosome

Chromatin loops

File:Emerging Evidence of Chromosome Folding by Loop Extrusion Supplemental Movie 1.webm

Animated representation of the dynamic formation of chromatin loops through CTCF (red) and condensin rings (yellow)^[9]

The beads-on-a-string chromatin structure has a tendency to form loops. These loops allow interactions between different regions of DNA by bringing them closer to each other, which increases the efficiency of gene interactions. This process is dynamic, with loops forming and disappearing. The loops are regulated by two main elements:^[10]

Cohesins, protein complexes that generate loops by extrusion of the DNA fiber through the ring-like structure of the complex itself.^[9]^[11]
CTCF, a transcription factor that limits the frontier of the DNA loop. To stop the growth of a loop, two CTCF molecules must be positioned in opposite directions to block the movement of the cohesin ring (see video).^[9]^[12]

There are many other elements involved. For example, Jpx regulates the binding sites of CTCF molecules along the DNA fiber.^[13]

TADs

see Topologically associating domain

Chromatin compartments

Chromatin compartments are large-scale structural domains of the genome that reflect the segregation of chromatin with similar transcriptional and epigenetic properties^[14]. Genome-wide chromosome conformation capture experiments have revealed that chromosomes are partitioned into at least two major compartment types, commonly referred to as A and B compartments. A compartments are generally enriched in transcriptionally active chromatin, open chromatin marks, and gene-rich regions, whereas B compartments are associated with transcriptionally inactive chromatin, heterochromatin, and interactions with nuclear structures such as the nuclear lamina. These compartments represent preferential long-range interactions between genomic regions with similar chromatin states and contribute to the spatial organization of chromosomes within the nucleus ^[15].

Chromosome territories

see Chromosome territories

Chromatin dynamics and regulation

Histone modifications

File:Basic units of chromatin structure.svg

Basic units of chromatin structure

Chromatin structure is highly dynamic and changes throughout the cell cycle and in response to cellular signals. Histone proteins play a central role in organizing chromatin and can undergo a wide range of post-translational modifications, including acetylation, methylation, phosphorylation, and ubiquitination (see histone modification). These modifications occur primarily on the flexible N-terminal tails of histones that extend outward from the nucleosome core.

The positively charged histone cores only partially counteract the negative charge of the DNA phosphate backbone resulting in a negative net charge of the overall structure. An imbalance of charge within the polymer causes electrostatic repulsion between neighboring chromatin regions that promote interactions with positively charged proteins, molecules, and cations. As these modifications occur, the electrostatic environment surrounding the chromatin will flux and the level of chromatin compaction will alter.^[3] The consequences in terms of chromatin accessibility and compaction depend both on the modified amino acid and the type of modification.

Different histone modifications are associated with distinct chromatin states. For example, histone acetylation is generally correlated with increased chromatin accessibility and active transcription, whereas certain histone methylation marks are associated with either transcriptional activation (trimethylation of histone H3 lysine 4) or repression trimethylation of histone H3, lysine 9 or lysine 27) depending on the modified residue.

Multiple histone modifications can occur simultaneously on the same nucleosome, creating combinations of regulatory signals sometimes referred to as the histone code. For example, developmental genes in mammalian embryonic stem cells often carry both activating (H3K4me3) and repressive (H3K27me3) marks in a configuration known as bivalent structure, which is involved into cell fate transtition during early mammalian development.

Polycomb-group proteins play a role in regulating genes through modulation of chromatin structure.^[16]

Enzymes that add, remove, or recognize histone modifications are often described as chromatin writers, erasers, and readers, respectively. For additional information, see Chromatin variant, Histone modifications in chromatin regulation and RNA polymerase control by chromatin structure.

Chromatin remodeling

see Chromatin remodeling

Transcriptional bursting

Main page: Transcriptional bursting

Chromatin and its interaction with enzymes has been researched, and a conclusion being made is that it is relevant and an important factor in gene expression. Vincent G. Allfrey, a professor at Rockefeller University, stated that RNA synthesis is related to histone acetylation.^[17] The lysine amino acid attached to the end of the histones is positively charged. The acetylation of these tails would make the chromatin ends neutral, allowing for DNA access.

When the chromatin decondenses, the DNA is open to entry of molecular machinery. Fluctuations between open and closed chromatin may contribute to the discontinuity of transcription, or transcriptional bursting. Other factors are probably involved, such as the association and dissociation of transcription factor complexes with chromatin. Specifically, RNA polymerase and transcriptional proteins have been shown to congregate into droplets via phase separation, and recent studies have suggested that 10 nm chromatin demonstrates liquid-like behavior increasing the targetability of genomic DNA.^[18] The interactions between linker histones and disordered tail regions act as an electrostatic glue organizing large-scale chromatin into a dynamic, liquid-like domain. Decreased chromatin compaction comes with increased chromatin mobility and easier transcriptional access to DNA.^[3] The phenomenon, as opposed to simple probabilistic models of transcription, can account for the high variability in gene expression occurring between cells in isogenic populations.^[19]

Structure of DNA

File:A-DNA, B-DNA and Z-DNA.png

The structures of A-, B-, and Z-DNA.

DNA can adopt several conformations, most commonly referred to as A-, B-, and Z-DNA. B-DNA is the predominant form found under physiological conditions and is the canonical right-handed double helix described by Watson and Crick. A-DNA is also a right-handed helix but is more compact and is typically observed under dehydrating conditions or in certain DNA–RNA hybrid structures.

Z-DNA differs from these forms in that it is a left-handed helix with a zigzag backbone^[20]. Transitions between B-DNA and Z-DNA can occur in regions experiencing high torsional stress, such as those generated during transcription. Because of these properties, Z-DNA has been proposed to play roles in chromatin organization and gene regulation.

Local DNA sequence composition and structural flexibility influence how DNA interacts with histone proteins and other chromatin-associated factors. For example, sequences enriched in adenine and thymine can bend more easily, affecting nucleosome positioning along the genome.

Chromatin during the cell cycle

Spatial organization of chromatin in the cell nucleus

The spatial arrangement of the chromatin within the nucleus is not random - specific regions of the chromatin can be found in certain territories. Territories are, for example, the lamina-associated domains (LADs), and the topologically associating domains (TADs), which are bound together by protein complexes.^[21] Polymer physics approaches have been widely used to model chromatin folding and genome organization. In particular, mechanisms such as loop extrusion, mediated by protein complexes including cohesin, have been proposed to explain the formation of chromatin loops and domain boundaries observed in chromosome conformation capture experiments.

Cell-cycle dependent structural organization

File:NHGRI human male karyotype.png

Karyogram of human male using Giemsa staining, showing the classic metaphase chromatin structure.

File:Condensation and resolution of human sister chromatids in early mitosis.svg

Condensation and resolution of human sister chromatids in early mitosis

Interphase: The structure of chromatin during interphase of mitosis is optimized to allow simple access of transcription and DNA repair factors to the DNA while compacting the DNA into the nucleus. The structure varies depending on the access required to the DNA. Genes that require regular access by RNA polymerase require the looser structure provided by euchromatin.
Metaphase: The metaphase structure of chromatin differs vastly to that of interphase. It is optimised for physical strength^{[citation needed]} and manageability, forming the classic chromosome structure seen in karyotypes. The structure of the condensed chromatin is thought to be loops of 30 nm fibre to a central scaffold of proteins. It is, however, not well-characterised. Chromosome scaffolds play an important role to hold the chromatin into compact chromosomes. Loops of 30 nm structure further condense with scaffold, into higher order structures.^[22] Chromosome scaffolds are made of proteins including condensin, type IIA topoisomerase and kinesin family member 4 (KIF4).^[23] The physical strength of chromatin is vital for this stage of division to prevent shear damage to the DNA as the daughter chromosomes are separated. To maximise strength the composition of the chromatin changes as it approaches the centromere, primarily through alternative histone H1 analogues. During mitosis, although most of the chromatin is tightly compacted, there are small regions that are not as tightly compacted. These regions often correspond to promoter regions of genes that were active in that cell type prior to chromatin formation. The lack of compaction of these regions is called bookmarking, which is an epigenetic mechanism believed to be important for transmitting to daughter cells the "memory" of which genes were active prior to entry into mitosis.^[24] This bookmarking mechanism is needed to help transmit this memory because transcription ceases during mitosis.

Specialized chromatin states

Sperm chromatin

During metazoan spermiogenesis, the spermatid's chromatin is remodeled into a more spaced-packaged, widened, almost crystal-like structure. This process is associated with the cessation of transcription and involves nuclear protein exchange. The histones are mostly displaced, and replaced by protamines (small, arginine-rich proteins).^[25] It is proposed that in yeast, regions devoid of histones become very fragile after transcription; HMO1, an HMG-box protein, helps in stabilizing nucleosomes-free chromatin.^[26]^[27]

Chromatin and DNA repair

A variety of internal and external agents can cause DNA damage in cells. Many factors influence how the repair route is selected, including the cell cycle phase and chromatin segment where the break occurred. In terms of initiating 5' end DNA repair, the p53 binding protein 1 (53BP1) and BRCA1 are important protein components that influence double-strand break repair pathway selection. The 53BP1 complex attaches to chromatin near DNA breaks and activates downstream factors such as Rap1-Interacting Factor 1 (RIF1) and shieldin, which protects DNA ends against nucleolytic destruction. DNA damage process occurs within the condition of chromatin, and the constantly changing chromatin environment has a large effect on it.^[28] Accessing and repairing the damaged cell of DNA, the genome condenses into chromatin and repairing it through modifying the histone residues. Through altering the chromatin structure, histones residues are adding chemical groups namely phosphate, acetyl and one or more methyl groups and these control the expressions of gene building by proteins to acquire DNA.^[29] Moreover, resynthesis of the delighted zone, DNA will be repaired by processing and restructuring the damaged bases. In order to maintain genomic integrity, "homologous recombination and classical non-homologous end joining process" has been followed by DNA to be repaired.^[30]

The packaging of eukaryotic DNA into chromatin presents a barrier to all DNA-based processes that require recruitment of enzymes to their sites of action.^[31] To allow the critical cellular process of DNA repair, the chromatin must be remodeled. In eukaryotes, ATP-dependent chromatin remodeling complexes and histone-modifying enzymes are two predominant factors employed to accomplish this remodeling process.^[32]

Chromatin relaxation occurs rapidly at the site of DNA damage.^[33] This process is initiated by PARP1 protein that starts to appear at DNA damage in less than a second, with half maximum accumulation within 1.6 seconds after the damage occurs.^[34] Next the chromatin remodeler Alc1 quickly attaches to the product of PARP1, and completes arrival at the DNA damage within 10 seconds of the damage.^[33] About half of the maximum chromatin relaxation, presumably due to action of Alc1, occurs by 10 seconds.^[33] This then allows recruitment of the DNA repair enzyme MRE11, to initiate DNA repair, within 13 seconds.^[34]

γH2AX, the phosphorylated form of H2AX is also involved in the early steps leading to chromatin decondensation after DNA damage occurrence. The histone variant H2AX constitutes about 10% of the H2A histones in human chromatin.^[35] γH2AX (H2AX phosphorylated on serine 139) can be detected as soon as 20 seconds after irradiation of cells (with DNA double-strand break formation), and half maximum accumulation of γH2AX occurs in one minute.^[35] The extent of chromatin with phosphorylated γH2AX is about two million base pairs at the site of a DNA double-strand break.^[35] γH2AX does not, itself, cause chromatin decondensation, but within 30 seconds of irradiation, RNF8 protein can be detected in association with γH2AX.^[36] RNF8 mediates extensive chromatin decondensation, through its subsequent interaction with CHD4,^[37] a component of the nucleosome remodeling and deacetylase complex NuRD.

After undergoing relaxation subsequent to DNA damage, followed by DNA repair, chromatin recovers to a compaction state close to its pre-damage level after about 20 min.^[33]

Methods to study chromatin

File:Heterochromatic versus euchromatic nuclei.jpg

Microscopy of heterochromatic versus euchromatic nuclei (H&E stain).

File:Well-differentiated neuroendocrine tumor with salt-and-pepper chromatin.png

Granular "salt-and-pepper chromatin", seen on H&E, Pap stain and comparison to actual salt and pepper. Its finding on microscopy indicates mainly medullary thyroid carcinoma, neuroendocrine tumours^[38] or pheochromocytoma.^[39]

File:Human karyotype with bands and sub-bands.png

Schematic karyogram of a human, showing an overview of the human genome using G banding, which is a method that includes Giemsa staining, wherein the lighter staining regions are generally more euchromatic (and more transcriptionally active), whereas darker regions generally are more heterochromatic.

ChIP-seq (Chromatin immunoprecipitation sequencing) is recognized as the vastly utilized chromatin identification method it has been using the antibodies that actively select, identify and combine with proteins including "histones, histone restructuring, transcription factors and cofactors". This has been providing data about the state of chromatin and the transcription of a gene by trimming "oligonucleotides" that are unbound.^[40] Chromatin immunoprecipitation sequencing aimed against different histone modifications, can be used to identify chromatin states throughout the genome. Different modifications have been linked to various states of chromatin.^[41]
DNase-seq (DNase I hypersensitive sites Sequencing) uses the sensitivity of accessible regions in the genome to the DNase I enzyme to map open or accessible regions in the genome.
FAIRE-seq (Formaldehyde-Assisted Isolation of Regulatory Elements sequencing) uses the chemical properties of protein-bound DNA in a two-phase separation method to extract nucleosome depleted regions from the genome.^[42]
ATAC-seq (Assay for Transposable Accessible Chromatin sequencing) uses the Tn5 transposase to integrate (synthetic) transposons into accessible regions of the genome consequentially highlighting the localisation of nucleosomes and transcription factors across the genome.
DNA footprinting is a method aimed at identifying protein-bound DNA. It uses labeling and fragmentation coupled to gel electrophoresis to identify areas of the genome that have been bound by proteins.^[43]
MNase-seq (Micrococcal Nuclease sequencing) uses the micrococcal nuclease enzyme to identify nucleosome positioning throughout the genome.^[44]^[45]
Chromosome conformation capture determines the spatial organization of chromatin in the nucleus, by inferring genomic locations that physically interact.
MACC profiling (Micrococcal nuclease ACCessibility profiling) uses titration series of chromatin digests with micrococcal nuclease to identify chromatin accessibility as well as to map nucleosomes and non-histone DNA-binding proteins in both open and closed regions of the genome.^[46]

Physical and topological properties

Chromatin knots

It has been a puzzle how decondensed interphase chromosomes remain essentially unknotted. The natural expectation is that in the presence of type II DNA topoisomerases that permit passages of double-stranded DNA regions through each other, all chromosomes should reach the state of topological equilibrium. The topological equilibrium in highly crowded interphase chromosomes forming chromosome territories would result in formation of highly knotted chromatin fibres. However, Chromosome Conformation Capture (3C) methods revealed that the decay of contacts with the genomic distance in interphase chromosomes is practically the same as in the crumpled globule state that is formed when long polymers condense without formation of any knots. To remove knots from highly crowded chromatin, one would need an active process that should not only provide the energy to move the system from the state of topological equilibrium but also guide topoisomerase-mediated passages in such a way that knots would be efficiently unknotted instead of making the knots even more complex. It has been shown that the process of chromatin-loop extrusion is ideally suited to actively unknot chromatin fibres in interphase chromosomes.^[47]

Notes

References

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↑ ^33.0 ^33.1 ^33.2 ^33.3 Sellou H, Lebeaupin T, Chapuis C, Smith R, Hegele A, Singh HR, Kozlowski M, Bultmann S, Ladurner AG, Timinszky G, Huet S (2016). "The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage". Mol. Biol. Cell. 27 (24): 3791–3799. doi:10.1091/mbc.E16-05-0269. PMC 5170603. PMID 27733626.
↑ ^34.0 ^34.1 Haince JF, McDonald D, Rodrigue A, Déry U, Masson JY, Hendzel MJ, Poirier GG (2008). "PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites". J. Biol. Chem. 283 (2): 1197–208. doi:10.1074/jbc.M706734200. PMID 18025084.
↑ ^35.0 ^35.1 ^35.2 Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (1998). "DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139". J. Biol. Chem. 273 (10): 5858–68. doi:10.1074/jbc.273.10.5858. PMID 9488723.
↑ Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, Lukas J (2007). "RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins". Cell. 131 (5): 887–900. doi:10.1016/j.cell.2007.09.040. PMID 18001824. S2CID 14232192.
↑ Luijsterburg MS, Acs K, Ackermann L, Wiegant WW, Bekker-Jensen S, Larsen DH, Khanna KK, van Attikum H, Mailand N, Dantuma NP (2012). "A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure". EMBO J. 31 (11): 2511–27. doi:10.1038/emboj.2012.104. PMC 3365417. PMID 22531782.
↑ Van Buren G, Rashid A, Yang AD, et al. (August 2007). "The development and characterization of a human midgut carcinoid cell line". Clin. Cancer Res. 13 (16): 4704–12. doi:10.1158/1078-0432.CCR-06-2723. PMID 17699847.
↑ Shidham VB, Galindo LM (1999). "Pheochromocytoma. Cytologic findings on intraoperative scrape smears in five cases". Acta Cytol. 43 (2): 207–13. doi:10.1159/000330978. PMID 10097711. S2CID 232277473.
↑ Small, Eliza C.; Maryanski, Danielle N.; Rodriguez, Keli L.; Harvey, Kevin J.; Keogh, Michael-C.; Johnstone, Andrea L. (2021), Posch, Anton (ed.), "Chromatin Immunoprecipitation (ChIP) to Study DNA–Protein Interactions", Proteomic Profiling, Methods in Molecular Biology, New York, NY: Springer US, 2261, pp. 323–343, doi:10.1007/978-1-0716-1186-9_20, ISBN 978-1-0716-1185-2, PMID 33420999, S2CID 231304041, retrieved 2022-10-24
↑ Rossi, M.J; Kuntala, P.K; Lai, W.K.M; et al. (10 March 2021). "A high-resolution protein architecture of the budding yeast genome". Nature. 592 (7853): 309–314. Bibcode:2021Natur.592..309R. doi:10.1038/s41586-021-03314-8. PMC 8035251. PMID 33692541.
↑ Giresi, Paul G.; Kim, Jonghwan; McDaniell, Ryan M.; Iyer, Vishwanath R.; Lieb, Jason D. (2007-06-01). "FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin". Genome Research. 17 (6): 877–885. doi:10.1101/gr.5533506. ISSN 1088-9051. PMC 1891346. PMID 17179217.
↑ Galas, D. J.; Schmitz, A. (1978-09-01). "DNAse footprinting: a simple method for the detection of protein-DNA binding specificity". Nucleic Acids Research. 5 (9): 3157–3170. doi:10.1093/nar/5.9.3157. ISSN 0305-1048. PMC 342238. PMID 212715.
↑ Cui, Kairong; Zhao, Keji (2012-01-01). "Genome-Wide Approaches to Determining Nucleosome Occupancy in Metazoans Using MNase-Seq". Chromatin Remodeling. Methods in Molecular Biology. 833. pp. 413–419. doi:10.1007/978-1-61779-477-3_24. ISBN 978-1-61779-476-6. ISSN 1940-6029. PMC 3541821. PMID 22183607.
↑ Buenrostro, Jason D.; Giresi, Paul G.; Zaba, Lisa C.; Chang, Howard Y.; Greenleaf, William J. (2013-12-01). "Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position". Nature Methods. 10 (12): 1213–1218. doi:10.1038/nmeth.2688. ISSN 1548-7105. PMC 3959825. PMID 24097267.
↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
↑ Racko D, Benedetti F, Goundaroulis D, Stasiak A (2018). "Chromatin Loop Extrusion and Chromatin Unknotting". Polymers. 10 (10): 1126–1137. doi:10.3390/polym10101126. PMC 6403842. PMID 30961051.

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External links

Chromatin, Histones & Cathepsin; PMAP The Proteolysis Map-animation
Nature journal: recent chromatin publications and news
Protocol for in vitro Chromatin Assembly
ENCODE threads Explorer Chromatin patterns at transcription factor binding sites. Nature (journal)

Template:Chromo Template:Nucleus

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[Racko_2018-47] Racko D, Benedetti F, Goundaroulis D, Stasiak A (2018). "Chromatin Loop Extrusion and Chromatin Unknotting". Polymers. 10 (10): 1126–1137. doi:10.3390/polym10101126. PMC 6403842. PMID 30961051.

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Chromatin: Difference between revisions

Latest revision as of 21:53, 19 May 2026

Contents

Basic chromatin structure

Nucleosomes

Historical 30-nm fiber model

Three-dimensional genome organization

Chromatin loops

TADs

Chromatin compartments

Chromosome territories

Chromatin dynamics and regulation

Histone modifications

Chromatin remodeling

Transcriptional bursting

Structure of DNA

Chromatin during the cell cycle

Spatial organization of chromatin in the cell nucleus

Cell-cycle dependent structural organization

Specialized chromatin states

Sperm chromatin

Chromatin and DNA repair

Methods to study chromatin

Physical and topological properties

Chromatin knots

See also

Notes

References

Additional sources

External links

Navigation menu

@@ Line 1: / Line 1: @@
 {{short description|Complex of DNA and protein in eukaryotic cells}}
-[[File:Chromatin Structures.png|thumb|360px|The major structures in DNA compaction: [[DNA]], the [[nucleosome]], the 11 nm [[beads on a string]] chromatin fibre and the [[metaphase]] [[chromosome]].]]
+[[File:Chromatin Structures.png|thumb|358x358px|The major structures in DNA compaction: [[DNA]], the [[nucleosome]], the 11 nm [[beads on a string]] chromatin fibre and the [[metaphase]] [[chromosome]].]]
-'''Chromatin''' is a complex of [[DNA]] and [[protein]] found in [[eukaryote|eukaryotic]] cells.<ref>{{cite journal|last1=Monday|first1=Tanmoy|title=Characterization of the RNA content of chromatin|journal=Genome Res.|date=July 2010 |volume=20 |issue=7 |pages=899–907 |pmc=2892091 |pmid=20404130 |doi=10.1101/gr.103473.109}}</ref> The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during [[cell division]], preventing [[DNA repair#DNA damage|DNA damage]], and regulating [[gene expression]] and [[DNA replication]]. During [[mitosis]] and [[meiosis]], chromatin facilitates proper segregation of the [[chromosome]]s in [[anaphase]]; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin.
+'''Chromatin''' is a complex of DNA and protein responsible for condensing and packaging chromosomal DNA. Chromatin is found in both bacterial<ref>{{Cite journal |last1=Hustmyer |first1=Christine M. |last2=Landick |first2=Robert |date=2024 |title=Bacterial chromatin proteins, transcription, and DNA topology: Inseparable partners in the control of gene expression |journal=Molecular Microbiology |language=en |volume=122 |issue=1 |pages=81-112 |doi=10.1111/mmi.15283}}</ref> and eukaryotic cells<ref>{{cite journal|last1=Monday|first1=Tanmoy|title=Characterization of the RNA content of chromatin|journal=Genome Res.|date=July 2010 |volume=20 |issue=7 |pages=899–907 |pmc=2892091 |pmid=20404130 |doi=10.1101/gr.103473.109}}</ref>. This article deals almost exclusively with eukaryotic chromatin.
-The primary protein components of chromatin are [[histone]]s. An [[octamer]] of two sets of four histone cores ([[Histone H2A]], [[Histone H2B]], [[Histone H3]], and [[Histone H4]]) bind to DNA and function as "anchors" around which the strands are wound.<ref name="doi.org">Maeshima, K., Ide, S., & Babokhov, M. (2019). Dynamic chromatin organization without the 30 nm fiber. ''Current opinion in cell biology, 58,'' 95–104. https://doi.org/10.1016/j.ceb.2019.02.003</ref> In general, there are three levels of chromatin organization:
+Eukaryotic chromatin consists primarily of DNA associated with histone proteins and numerous other chromatin-binding factors that contribute to genome organization and regulation. Chromatin packages long DNA molecules into compact structures while controlling access to genetic information for processes such as transcription, DNA replication, and DNA repair. During cell division, chromatin facilitates proper segregation of chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin.
-# DNA wraps around histone proteins, forming [[nucleosome]]s and the so-called [[beads on a string]] structure ([[euchromatin]]).
+Chromatin organization is often described at several structural levels. At the most basic level, DNA wrapped around histone octamers forms nucleosomes connected by stretches of linker DNA, producing a structure sometimes referred to as a “beads-on-a-string” fiber approximately 10–11 nm in diameter. Nucleosome arrays can interact with each other and with linker histones to form higher-order chromatin structures. 30-nm chromatin fiber has been observed ''in vitro'', although its presence and prevalence in living cells remain debated<ref name="doi.org">{{Cite journal |last=Maeshima |first=Kazuhiro |last2=Ide |first2=Satoru |last3=Babokhov |first3=Michael |date=2019-06-01 |title=Dynamic chromatin organization without the 30-nm fiber |url=https://www.sciencedirect.com/science/article/pii/S0955067418301881 |journal=Current Opinion in Cell Biology |series=Cell Nucleus |volume=58 |pages=95–104 |doi=10.1016/j.ceb.2019.02.003 |issn=0955-0674|doi-access=free }}</ref>.
-# Multiple histones wrap into a 30-[[nanometer]] fiber consisting of nucleosome arrays in their most compact form ([[heterochromatin]]).{{efn|Though it has been definitively established to exist ''in vitro'', the 30-[[nanometer]] fibre was not seen in recent X-ray studies of human mitotic chromosomes.<ref>{{cite journal |last=Hansen |first=Jeffrey |title=Human mitotic chromosome structure: what happened to the 30-nm fibre? |journal=The EMBO Journal |date=March 2012 |volume=31 |pages=1621–1623 |doi=10.1038/emboj.2012.66 |pmid=22415369 |issue=7 |pmc=3321215}}</ref>}}
-# Higher-level [[DNA supercoiling]] of the 30&nbsp;nm fiber produces the [[metaphase]] chromosome (during mitosis and meiosis).
-Many organisms, however, do not follow this organization scheme. For example, [[spermatozoa]] and [[Bird|avian]] [[red blood cell]]s have more tightly packed chromatin than most eukaryotic cells, and [[trypanosomatid]] [[protozoa]] do not [[DNA condensation|condense]] their chromatin into visible chromosomes at all. [[Prokaryotic]] cells have entirely different structures for organizing their DNA (the prokaryotic chromosome equivalent is called a [[genophore]] and is localized within the [[nucleoid]] region).
+At larger genomic scales, chromatin is organized into loops and domains that contribute to the three-dimensional architecture of the genome. Chromosomes are further partitioned into compartments associated with active (euchromatin) or inactive (heterochromatin) chromatin states, and individual chromosomes occupy distinct spatial regions within the nucleus known as chromosome territories.
-The overall structure of the chromatin network further depends on the stage of the [[cell cycle]]. During [[interphase]], the chromatin is structurally loose to allow access to [[RNA polymerase|RNA]] and [[DNA polymerase]]s that [[transcription (biology)|transcribe]] and replicate the DNA. The local structure of chromatin during interphase depends on the specific [[gene]]s present in the DNA. Regions of DNA containing genes which are actively transcribed ("turned on") are less tightly compacted and closely associated with RNA polymerases in a structure known as [[euchromatin]], while regions containing inactive genes ("turned off") are generally more condensed and associated with structural proteins in [[heterochromatin]].<ref>
+Many organisms exhibit variations in chromatin organization. For example, spermatozoa and avian red blood cells have more tightly packed chromatin than most eukaryotic cells. In contrast, some protozoa such as [[trypanosomatid]] do not DNA condense their chromatin into visible chromosomes at all.
-{{cite journal |author=Dame, R.T. |s2cid=26965112 |title=The role of nucleoid-associated proteins in the organization and compaction of bacterial chromatin |journal=[[Molecular Microbiology (journal)|Molecular Microbiology]] |volume=56 |issue=4 |pages=858–870 |date=May 2005 |pmid=15853876 |doi=10.1111/j.1365-2958.2005.04598.x|doi-access= }}</ref> [[Epigenetic]] modification of the structural proteins in chromatin via [[methylation]] and [[acetylation]] also alters local chromatin structure and therefore gene expression. There is limited understanding of chromatin structure and it is active area of research in [[molecular biology]].
-==Dynamic chromatin structure and hierarchy==
+Bacteria organize their DNA differently, forming a chromatin or nucleoid structure organized by nucleoid-associated proteins including H-NS and StpA<ref>{{Cite journal |last=Gavrilov |first=Alexey A. |last2=Shamovsky |first2=Ilya |last3=Zhegalova |first3=Irina |last4=Proshkin |first4=Sergey |last5=Shamovsky |first5=Yosef |last6=Evko |first6=Grigory |last7=Epshtein |first7=Vitaly |last8=Rasouly |first8=Aviram |last9=Blavatnik |first9=Anna |last10=Lahiri |first10=Sudipta |last11=Rothenberg |first11=Eli |last12=Razin |first12=Sergey V. |last13=Nudler |first13=Evgeny |date=September 2025 |title=Elementary 3D organization of active and silenced E. coli genome |url=https://www.nature.com/articles/s41586-025-09396-y |journal=Nature |language=en |volume=645 |issue=8082 |pages=1060–1070 |doi=10.1038/s41586-025-09396-y |issn=1476-4687|pmc=12460168 }}</ref>. Some archaeal species encode histone proteins, and package DNA into nucleosome-like assemblies of variable size, sometimes referred to as hypernucleosomes.<ref>{{cite journal | last1=Mattiroli | first1=Francesca | last2=Bhattacharyya | first2=Sudipta | last3=Dyer | first3=Pamela N. | last4=White | first4=Alison E. | last5=Sandman | first5=Kathleen | last6=Burkhart | first6=Brett W. | last7=Byrne | first7=Kyle R. | last8=Lee | first8=Thomas | last9=Ahn | first9=Natalie G. | last10=Santangelo | first10=Thomas J. | last11=Reeve | first11=John N. | last12=Luger | first12=Karolin | title=Structure of histone-based chromatin in Archaea | journal=Science | year=2017 | volume=357 | issue=6351 | pages=609–612 | doi=10.1126/science.aaj1849 | pmid=28798133 }}</ref><ref>{{cite journal | last1=Ranawat | first1=Harsh M. | last2=Cajili | first2=Marc K. | last3=Lopez-Barbosa | first3=Natalia | last4=Quail | first4=Thomas | last5=Dame | first5=Remus T. | last6=Dodonova | first6=Svetlana O. | title=Cryo-EM reveals open and closed Asgard chromatin assemblies | journal=Molecular Cell | year=2025 | doi=10.1016/j.molcel.2025.10.001 | pmid=41161312 | doi-access=free | hdl=1887/4281705 | hdl-access=free }}</ref>
-[[File:Basic units of chromatin structure.svg|thumb|Basic units of chromatin structure]]
-[[File:Chromosome en.svg|thumb|the structure of chromatin within a chromosome]]
-Chromatin undergoes various structural changes during a [[cell cycle]]. [[Histone]] proteins are the basic packers and arrangers of chromatin and can be modified by various post-translational modifications to alter chromatin packing ([[histone modification]]). Most modifications occur on histone tails. The positively charged histone cores only partially counteract the negative charge of the DNA phosphate backbone resulting in a negative net charge of the overall structure. An imbalance of charge within the polymer causes [[electrostatic]] repulsion between neighboring chromatin regions that promote interactions with positively charged proteins, molecules, and cations. As these modifications occur, the electrostatic environment surrounding the chromatin will flux and the level of chromatin compaction will alter.<ref name="doi.org"/> The consequences in terms of chromatin accessibility and compaction depend both on the modified amino acid and the type of modification. For example, [[histone acetylation and deacetylation|histone acetylation]] results in loosening and increased accessibility of chromatin for replication and transcription. Lysine trimethylation can either lead to increased transcriptional activity ([[H3K4me3|trimethylation of histone H3 lysine 4]]) or transcriptional repression and chromatin compaction ([[H3K9me3|trimethylation of histone H3, lysine 9]] or [[H3K27me3|lysine 27]]). Several studies suggested that different modifications could occur simultaneously. For example, it was proposed that a [[bivalent chromatin|bivalent]] structure (with trimethylation of both lysine 4 and 27 on histone H3) is involved in early mammalian development. Another study tested the role of [[H4K16ac|acetylation of histone 4 on lysine 16]] on chromatin structure and found that [[homogeneous]] acetylation inhibited 30&nbsp;nm chromatin formation and blocked [[adenosine triphosphate]] remodeling. This singular modification changed the dynamics of the chromatin which shows that acetylation of H4 at K16 is vital for proper intra- and inter- functionality of chromatin structure.<ref>Shogren-Knaak, M., Ishii, H., Sun, J. M., Pazin, M. J., Davie, J. R., & Peterson, C. L. (2006). Histone H4-K16 acetylation controls chromatin structure and protein interactions. ''Science, 311''(5762), 844–847. https://doi.org/10.1126/science.1124000</ref>
-<ref>
-{{cite journal
-|title= A bivalent chromatin structure marks key developmental genes in embryonic stem cells
-|vauthors = Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES
-|journal= [[Cell (journal)|Cell]]
-|date= April 2006
-|volume= 125
-|issue= 2
-|pages= 315–26
-|pmid= 16630819
-|issn= 0092-8674
-|doi= 10.1016/j.cell.2006.02.041|s2cid = 9993008
-|doi-access= free
-}}
-</ref>
-[[Polycomb-group proteins]] play a role in regulating genes through modulation of chromatin structure.<ref name= Portoso >{{cite book |chapter-url=http://www.horizonpress.com/rnareg|vauthors=Portoso M, Cavalli G|year=2008|chapter=The Role of RNAi and Noncoding RNAs in Polycomb Mediated Control of Gene Expression and Genomic Programming|title=RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity|publisher=Caister Academic Press|isbn=978-1-904455-25-7}}</ref>
+Chromatin organization also varies throughout the cell cycle. During interphase, chromatin is generally less condensed, allowing access to RNA and DNA polymerases that transcribe and replicate the DNA. The local structure of chromatin during interphase depends on the specific genes present in the DNA.
-For additional information, see [[Chromatin variant]], [[Histone#Histone modifications in chromatin regulation|Histone modifications in chromatin regulation]] and [[RNA polymerase control by chromatin structure#RNA polymerase control by chromatin structure|RNA polymerase control by chromatin structure]].
+During mitosis and meiosis, chromatin becomes highly compacted to facilitate the segregation of chromosomes. Within interphase nuclei, genomic regions differ in their degree of compaction and transcriptional activity. Actively transcribed regions are often associated with less condensed chromatin known as euchromatin, whereas transcriptionally inactive or repressed regions are frequently enriched in more compact heterochromatin.<ref>
+{{cite journal |author=Dame, R.T. |s2cid=26965112 |title=The role of nucleoid-associated proteins in the organization and compaction of bacterial chromatin |journal=[[Molecular Microbiology (journal)|Molecular Microbiology]] |volume=56 |issue=4 |pages=858–870 |date=May 2005 |pmid=15853876 |doi=10.1111/j.1365-2958.2005.04598.x|doi-access= }}</ref> Chemical modifications of chromatin components, often so-called epigenetic modification, including histone tails methylation and acetylation also alters local chromatin structure and therefore gene expression.
-===Structure of DNA===
+== Basic chromatin structure ==
-[[File:A-DNA, B-DNA and Z-DNA.png|thumb|left|300px|The structures of A-, B-, and Z-DNA.]]
-{{main|Mechanical properties of DNA|Z-DNA}}
+===Nucleosomes===
-In nature, DNA can form three structures, [[A-DNA|A-]], [[B-DNA|B-]], and [[Z-DNA]]. A- and B-DNA are very similar, forming right-handed helices, whereas Z-DNA is a left-handed helix with a zig-zag phosphate backbone. Z-DNA is thought to play a specific role in chromatin structure and transcription because of the properties of the junction between B- and Z-DNA.
+{{Main|Nucleosome|Chromatosome|Histone}}
+The primary protein components of chromatin are [[histone]]s. [[Nucleosome]], the fundamental basic unit of chromatin, consists of DNA wrapped around a histone [[octamer]] containing two copies each of the core histones [[Histone H2A]], [[Histone H2B]], [[Histone H3]], and [[Histone H4]].<ref name="doi.org" /> Approximately 147 base pairs of DNA wrap around this histone octamer to form the nucleosome core particle.[[File:Nucleosome 1KX5 2.png|thumb|left|194x194px|A cartoon representation of the nucleosome structure. From {{PDB|1KX5}}.]]
+Neighboring nucleosomes are connected by stretches of [[linker DNA]], which vary in length among organisms and cell types but typically range from about 20 to 60 base pairs. Arrays of nucleosomes connected by linker DNA form an extended fiber often described as a “beads-on-a-string” structure approximately 10–11 nm in diameter under low-salt or experimentally reconstituted conditions.
+In addition to core histones, a linker [[histone H1]] binds near the entry and exit sites of DNA on the nucleosome and contributes to higher-order chromatin organization. The nucleosome core particle, together with histone H1, is known as a [[chromatosome]].
+The nucleosomes bind DNA non-specifically, as required by their function in general DNA packaging.  There are, however, large DNA sequence preferences that govern nucleosome positioning.  This is due primarily to the varying physical properties of different DNA sequences: For instance, [[adenine]] (A),  and [[thymine]] (T) is more favorably compressed into the inner minor grooves. This means nucleosomes can bind preferentially at one position approximately every 10 base pairs (the helical repeat of DNA)- where the DNA is rotated to maximize the number of A and T bases that will lie in the inner minor groove (see [[nucleic acid structure]]).
+=== Historical 30-nm fiber model ===
+[[File:30nm Chromatin Structures.png|thumb|right|206x206px|"solenoid" structure and loose helix structure of historical 30 nm fiber]]
+Under certain experimental conditions, nucleosome arrays can fold into more compact structures with diameters of approximately 30 nm. Early models proposed that chromatin fibers adopt regular helical arrangements, including a one-start solenoid model and a two-start zigzag model.
+However, the existence of a uniform 30-nm chromatin fiber in living cells remains debated. Studies using cryo-electron microscopy<ref>{{Cite journal |last=Ou |first=Horng |title=ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and mitotic cells |url=https://www.science.org/doi/10.1126/science.aag0025 |journal=Science |volume=357 |issue=6349}}</ref> and other high-resolution imaging methods have suggested that chromatin in many cell types forms irregular and dynamic nucleosome assemblies rather than regular 30-nm fibers<ref name="doi.org" />.
+== Three-dimensional genome organization ==
+see [[Nuclear organization]][[File:Chromosome en.svg|thumb|the structure of chromatin within a chromosome]]
+===Chromatin loops===
+[[File:Emerging_Evidence_of_Chromosome_Folding_by_Loop_Extrusion_Supplemental_Movie_1.webm|thumb|Animated representation of the dynamic formation of chromatin loops through [[CTCF]] (red) and [[condensin]] rings (yellow)<ref name="Emerging Loop Extrusion">{{cite journal|vauthors=Fudenberg G, Abdennur N, Imakaev M, Goloborodko A, Mirny LA|title=Emerging Evidence of Chromosome Folding by Loop Extrusion|journal=Cold Spring Harbor Symposia on Quantitative Biology|date=2017|volume=82|pages=45–55|doi=10.1101/sqb.2017.82.034710|pmid=29728444|pmc=6512960}}</ref>]]
+The beads-on-a-string chromatin structure has a tendency to form loops. These loops allow interactions between different regions of DNA by bringing them closer to each other, which increases the efficiency of gene interactions. This process is dynamic, with loops forming and disappearing. The loops are regulated by two main elements:<ref>{{cite journal|vauthors=Kadauke S, Blobel GA|date=2009|title=Chromatin loops in gene regulation|journal=Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms |volume=1789|issue=1|pages=17–25|doi=10.1016/j.bbagrm.2008.07.002|pmid=18675948 |pmc=2638769 }}</ref>
+* [[Cohesin]]s, [[protein complex]]es that generate loops by extrusion of the DNA fiber through the ring-like structure of the complex itself.<ref name="Emerging Loop Extrusion" /><ref>{{Cite journal |last1=Davidson |first1=Iain F. |last2=Bauer |first2=Benedikt |last3=Goetz |first3=Daniela |last4=Tang |first4=Wen |last5=Wutz |first5=Gordana |last6=Peters |first6=Jan-Michael |date=2019-12-13 |title=DNA loop extrusion by human cohesin |url=https://www.science.org/doi/10.1126/science.aaz3418 |journal=Science |language=en |volume=366 |issue=6471 |pages=1338–1345 |doi=10.1126/science.aaz3418 |pmid=31753851 |bibcode=2019Sci...366.1338D |issn=0036-8075|url-access=subscription }}</ref>
+* [[CTCF]], a [[transcription factor]] that limits the frontier of the DNA loop. To stop the growth of a loop, two CTCF molecules must be positioned in opposite directions to block the movement of the cohesin ring (''see video'').<ref name="Emerging Loop Extrusion" /><ref>{{Cite journal |last1=Busslinger |first1=Georg A. |last2=Stocsits |first2=Roman R. |last3=van der Lelij |first3=Petra |last4=Axelsson |first4=Elin |last5=Tedeschi |first5=Antonio |last6=Galjart |first6=Niels |last7=Peters |first7=Jan-Michael |date=April 2017 |title=Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl |journal=Nature |language=en |volume=544 |issue=7651 |pages=503–507 |doi=10.1038/nature22063 |issn=0028-0836 |pmc=6080695 |pmid=28424523 |bibcode=2017Natur.544..503B }}</ref>
+There are many other elements involved. For example, [[Jpx (gene)|Jpx]] regulates the binding sites of CTCF molecules along the DNA fiber.<ref>{{cite journal|vauthors=Oh HJ, Aguilar R, Kesner B, Lee HG, Kriz AJ, Chu HP, Lee JT|title=Jpx RNA regulates CTCF anchor site selection and formation of chromosome loops|journal=Cell|volume=184|issue=25|date=2021|pages=6157–6173|issn=0092-8674|doi=10.1016/j.cell.2021.11.012|pmid=34856126 |pmc=8671370 }}</ref>
+=== TADs ===
+see [[Topologically associating domain]]
+=== Chromatin compartments ===
+Chromatin compartments are large-scale structural domains of the genome that reflect the segregation of chromatin with similar transcriptional and epigenetic properties<ref>{{Cite journal |last=Lieberman-Aiden |first=Erez |last2=van Berkum |first2=Nynke L. |last3=Williams |first3=Louise |last4=Imakaev |first4=Maxim |last5=Ragoczy |first5=Tobias |last6=Telling |first6=Agnes |last7=Amit |first7=Ido |last8=Lajoie |first8=Bryan R. |last9=Sabo |first9=Peter J. |last10=Dorschner |first10=Michael O. |last11=Sandstrom |first11=Richard |last12=Bernstein |first12=Bradley |last13=Bender |first13=M. A. |last14=Groudine |first14=Mark |last15=Gnirke |first15=Andreas |date=2009-10-09 |title=Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome |url=https://www.science.org/doi/10.1126/science.1181369 |journal=Science |language=en |volume=326 |issue=5950 |pages=289–293 |doi=10.1126/science.1181369 |issn=0036-8075 |pmc=2858594 |pmid=19815776}}</ref>. Genome-wide chromosome conformation capture experiments have revealed that chromosomes are partitioned into at least two major compartment types, commonly referred to as A and B compartments. A compartments are generally enriched in transcriptionally active chromatin, open chromatin marks, and gene-rich regions, whereas B compartments are associated with transcriptionally inactive chromatin, heterochromatin, and interactions with nuclear structures such as the nuclear lamina. These compartments represent preferential long-range interactions between genomic regions with similar chromatin states and contribute to the spatial organization of chromosomes within the nucleus <ref>{{Cite journal |last=Rowley |first=M. Jordan |last2=Corces |first2=Victor G. |date=December 2018 |title=Organizational principles of 3D genome architecture |url=https://www.nature.com/articles/s41576-018-0060-8 |journal=Nature Reviews Genetics |language=en |volume=19 |issue=12 |pages=789–800 |doi=10.1038/s41576-018-0060-8 |issn=1471-0056 |pmc=6312108 |pmid=30367165}}</ref>.
+=== Chromosome territories ===
+see [[Chromosome territories]]
+== Chromatin dynamics and regulation ==
-At the junction of B- and Z-DNA, one pair of bases is flipped out from normal bonding. These play a dual role of a site of recognition by many proteins and as a sink for torsional stress from [[RNA polymerase]] or nucleosome binding. DNA bases are stored as a code structure with four chemical bases such as ''"Adenine (A), Guanine (G), Cytosine (C), and Thymine (T)"''. The order and sequences of these chemical structures of DNA are reflected as information available for the creation and control of human organisms. ''"A with T and C with G"'' pairing up to build the DNA base pair. ''Sugar and phosphate'' molecules are also paired with these bases, making DNA nucleotides arrange 2 long spiral strands unitedly called ''"double helix"''.<ref>{{Cite journal |last=Neidle |first=Stephen |date=January 2021 |title=Beyond the double helix: DNA structural diversity and the PDB |journal=Journal of Biological Chemistry |language=en |volume=296 |pages=100553 |doi=10.1016/j.jbc.2021.100553|pmid=33744292 |pmc=8063756 |doi-access=free }}</ref> In eukaryotes, DNA consists of a cell nucleus and the DNA is providing strength and direction to the mechanism of heredity. Moreover, between the nitrogenous bonds of the 2 DNA, homogenous bonds are forming.
+=== Histone modifications ===
+[[File:Basic units of chromatin structure.svg|thumb|Basic units of chromatin structure]]Chromatin structure is highly dynamic and changes throughout the [[cell cycle]] and in response to cellular signals. [[Histone]]  proteins play a central role in organizing chromatin and can undergo a wide range of post-translational modifications, including acetylation, methylation, phosphorylation, and ubiquitination (see [[histone modification]]). These modifications occur primarily on the flexible N-terminal tails of histones that extend outward from the nucleosome core.
-<ref>{{Cite journal |last1=Minchin |first1=Steve |last2=Lodge |first2=Julia |date=2019-10-16 |title=Understanding biochemistry: structure and function of nucleic acids |url=https://portlandpress.com/essaysbiochem/article/63/4/433/220684/Understanding-biochemistry-structure-and-function |journal=Essays in Biochemistry |language=en |volume=63 |issue=4 |pages=433–456 |doi=10.1042/EBC20180038 |pmid=31652314 |pmc=6822018 |issn=0071-1365}}</ref><!---
+The positively charged histone cores only partially counteract the negative charge of the DNA phosphate backbone resulting in a negative net charge of the overall structure. An imbalance of charge within the polymer causes [[electrostatic]] repulsion between neighboring chromatin regions that promote interactions with positively charged proteins, molecules, and cations. As these modifications occur, the electrostatic environment surrounding the chromatin will flux and the level of chromatin compaction will alter.<ref name="doi.org" /> The consequences in terms of chromatin accessibility and compaction depend both on the modified amino acid and the type of modification.
- Move to [[mechanical properties of DNA]] or [[Z-DNA]]? "===DNA structure===
-[[File:B&Z&A DNA formula.jpg|thumb|right|200px|'''Fig. 2:''' Alternative structural forms of DNA influencing chromatin structure]]
-===Chromatin and Watson/Crick base pairing===
+Different histone modifications are associated with distinct chromatin states. For example, [[histone acetylation and deacetylation|histone acetylation]] is generally correlated with increased chromatin accessibility and active transcription, whereas certain histone methylation marks are associated with either transcriptional activation  ([[H3K4me3|trimethylation of histone H3 lysine 4]]) or repression [[H3K9me3|trimethylation of histone H3, lysine 9]] or [[H3K27me3|lysine 27]]) depending on the modified residue.
-Crick and Watson's famous structure of [[DNA]] (called B-DNA) is only one of three possible structural forms (Fig. 2).
-For the C-N bond between a base and its sugar, there are two different conformations. The anti-conformation occurs in all A- and B-DNAs as well as in Z-DNA where a Cytosine is present.
+Multiple histone modifications can occur simultaneously on the same nucleosome, creating combinations of regulatory signals sometimes referred to as the ''histone code''. For example, developmental genes in mammalian embryonic stem cells often carry both activating (H3K4me3) and repressive (H3K27me3) marks in a configuration known as [[bivalent chromatin|bivalent]] structure, which is involved into cell fate transtition during early mammalian development.
-In case of a Guanine, Z-DNA takes the syn-conformation. The periodic change between a purine and pyrimidine along the strand of a Z-DNA accomplishes the alternating syn-anti-conformation characteristic of the zigzag structure of the Z-DNA helix. The yellow circles designated A, B, Z indicate the axes of the three possible types of DNA (Fig. 2).
-[[File:B&Z junction DNA.jpg|thumb|200px|'''Fig. 3:''' Structure of DNA with two B-Z DNA junctions: It encompasses 1. breakage of a hydrogen-bond, where a Guanine rotates around its glycosyl-bond and the sugar thereby transforms into its syn-conformation. 2. Rotation of the corresponding second base (Cytosine) involving rotation of the sugar around the sugar-phosphate-bond. 3. At the B-Z junction hydrogen-bonds remain broken and bases are extruded.]]
+[[Polycomb-group proteins]] play a role in regulating genes through modulation of chromatin structure.<ref name="Portoso">{{cite book|chapter-url=http://www.horizonpress.com/rnareg|vauthors=Portoso M, Cavalli G|year=2008|chapter=The Role of RNAi and Noncoding RNAs in Polycomb Mediated Control of Gene Expression and Genomic Programming|title=RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity|publisher=Caister Academic Press|isbn=978-1-904455-25-7|archive-date=2012-01-02|access-date=2009-12-18|archive-url=https://web.archive.org/web/20120102091412/http://www.horizonpress.com/rnareg|url-status=dead}}</ref>
-===Junction between B- and Z-DNA===
+Enzymes that add, remove, or recognize histone modifications are often described as chromatin writers, erasers, and readers, respectively. For additional information, see [[Chromatin variant]], [[Histone#Histone modifications in chromatin regulation|Histone modifications in chromatin regulation]] and [[RNA polymerase control by chromatin structure#RNA polymerase control by chromatin structure|RNA polymerase control by chromatin structure]].
-Chromatin regions near the transcription start site frequently contain DNA sequence motifs favourable for forming Z-DNA. Likewise, formation of Z-DNA near the promoter region stimulates transcription. Z-DNA is stabilized by binding specific proteins. Formation of Z-DNA from B-DNA is a dynamic process wherein B-DNA is the relaxed state. When a Z-DNA segment is formed two B-Z junctions form (Fig.3). The crystal structure of such junctions is known. At each junction, the hydrogen bonds between a Watson/Crick base pair is broken and the bases are extruded. Extrusion of a base from the helix is a well-known reaction performed by enzymes (i.e., DNA glycosylase) that edit or repair DNA during Base Excision Repair (BER). Crystal structures of extruded bases co-crystallized with Hha1 methyltransferase, human DNA repair protein AGT(O(6)-alkylguanine-DNAalkyltransferase), or bacteriophage T4 endonuclease V are similar to the extruded bases at B-Z junctions. Z-DNA may also provide a sink to absorb torsional strain following an RNA polymerase or a transient nucleosome. Also, Z-DNA may represent a signal for the recruitment of RNA-editing enzymes. It is possible that chromatin encompassing Z-DNA segments also affect replication." --->
-===Nucleosomes and beads-on-a-string===
+=== Chromatin remodeling ===
-{{Main|Nucleosome|Chromatosome|Histone}}
+see [[Chromatin remodeling]]
-[[File:Nucleosome 1KX5 2.png|thumb|left|150px|A cartoon representation of the nucleosome structure. From {{PDB|1KX5}}.]]
-The basic repeat element of chromatin is the nucleosome, interconnected by sections of [[linker DNA]], a far shorter arrangement than pure DNA in solution.
-In addition to core histones, a linker [[histone H1]] exists that contacts the exit/entry of the DNA strand on the nucleosome. The nucleosome core particle, together with histone H1, is known as a [[chromatosome]].  Nucleosomes, with about 20 to 60 base pairs of linker DNA, can form, under non-physiological conditions, an approximately 11&nbsp;nm [[beads on a string]] fibre.
+=== Transcriptional bursting ===
+<blockquote>''Main page: [[Transcriptional bursting]]''</blockquote>Chromatin and its interaction with enzymes has been researched, and a conclusion being made is that it is relevant and an important factor in gene expression. Vincent G. Allfrey, a professor at Rockefeller University, stated that RNA synthesis is related to histone acetylation.<ref name="pmid14172992">{{cite journal |vauthors=Allfrey VG, Faulkner R, Mirsky AE |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=51 |issue= 5|pages=786–94 |date=May 1964 |pmid=14172992 |pmc=300163 |doi= 10.1073/pnas.51.5.786|bibcode=1964PNAS...51..786A |title=Acetylation and Methylation of Histones and Their Possible Role in the Regulation of RNA Synthesis |doi-access=free }}</ref> The lysine amino acid attached to the end of the histones is positively charged. The acetylation of these tails would make the chromatin ends neutral, allowing for DNA access.
-The nucleosomes bind DNA non-specifically, as required by their function in general DNA packaging.  There are, however, large DNA sequence preferences that govern nucleosome positioning.  This is due primarily to the varying physical properties of different DNA sequences: For instance, [[adenine]] (A),  and [[thymine]] (T) is more favorably compressed into the inner minor grooves. This means nucleosomes can bind preferentially at one position approximately every 10 base pairs (the helical repeat of DNA)- where the DNA is rotated to maximise the number of A and T bases that will lie in the inner minor groove. (See [[nucleic acid structure]].)
+When the chromatin decondenses, the DNA is open to entry of molecular machinery. Fluctuations between open and closed chromatin may contribute to the discontinuity of transcription, or [[transcriptional bursting]].  Other factors are probably involved, such as the association and dissociation of transcription factor complexes with chromatin. Specifically, RNA polymerase and transcriptional proteins have been shown to congregate into droplets via phase separation, and recent studies have suggested that 10&nbsp;nm chromatin demonstrates liquid-like behavior increasing the targetability of genomic DNA.<ref>Maeshima, K., Ide, S., Hibino, K., & Sasai, M. (2016). Liquid-like behavior of chromatin. ''Current opinion in genetics & development, 37,'' 36–45. https://doi.org/10.1016/j.gde.2015.11.006</ref> The interactions between linker histones and disordered tail regions act as an electrostatic glue organizing large-scale chromatin into a dynamic, liquid-like domain. Decreased chromatin compaction comes with increased chromatin mobility and easier transcriptional access to DNA.<ref name="doi.org" /> The phenomenon, as opposed to simple probabilistic models of transcription, can account for the high variability in gene expression occurring between cells in isogenic populations.<ref name="pmid22944281">{{cite journal |vauthors=Kaochar S, Tu BP |title=Gatekeepers of chromatin: Small metabolites elicit big changes in gene expression |journal=Trends Biochem. Sci. |volume=37 |issue=11 |pages=477–83 |date=November 2012 |pmid=22944281 |pmc=3482309 |doi=10.1016/j.tibs.2012.07.008 }}</ref>
-===30-nm chromatin fiber in mitosis===
+===Structure of DNA===
-[[File:30nm Chromatin Structures.png|thumb|right|307x307px|Two proposed structures of the 30 nm chromatin filament. <br />Left: 1 start helix "solenoid" structure. <br />Right: 2 start loose helix structure. <br />Note: the histones are omitted in this diagram - only the DNA is shown.]]
+{{main|Mechanical properties of DNA|Z-DNA}}
-With addition of H1, during [[mitosis]] the [[Beads on a string|beads-on-a-string structure]] can coil into a 30&nbsp;nm-diameter helical structure known as the 30&nbsp;nm fibre or filament. The precise structure of the chromatin fiber in the cell is not known in detail.<ref>{{cite web|last1=Annunziato|first1=Anthony T.|title=DNA Packaging: Nucleosomes and Chromatin|url=http://www.nature.com/scitable/topicpage/dna-packaging-nucleosomes-and-chromatin-310|website=Scitable|publisher=Nature Education|access-date=2015-10-29}}</ref>
+[[File:A-DNA, B-DNA and Z-DNA.png|thumb|left|196x196px|The structures of A-, B-, and Z-DNA.]]
+DNA can adopt several conformations, most commonly referred to as [[A-DNA|A-]], [[B-DNA|B-]], and [[Z-DNA]]. B-DNA is the predominant form found under physiological conditions and is the canonical right-handed double helix described by Watson and Crick. A-DNA is also a right-handed helix but is more compact and is typically observed under dehydrating conditions or in certain DNA–RNA hybrid structures.
-This level of chromatin structure is thought to be the form of [[heterochromatin]], which contains mostly transcriptionally silent genes. Electron microscopy studies have demonstrated that the 30&nbsp;nm fiber is highly dynamic such that it unfolds into a 10&nbsp;nm fiber beads-on-a-string structure when transversed by an RNA polymerase engaged in transcription.
+Z-DNA differs from these forms in that it is a left-handed helix with a zigzag backbone<ref>{{Cite journal |last=Rich |first=Alexander |last2=Zhang |first2=Shuguang |date=July 2003 |title=Z-DNA: the long road to biological function |url=https://www.nature.com/articles/nrg1115 |journal=Nature Reviews Genetics |language=en |volume=4 |issue=7 |pages=566–572 |doi=10.1038/nrg1115 |issn=1471-0064|url-access=subscription }}</ref>. Transitions between B-DNA and Z-DNA can occur in regions experiencing high torsional stress, such as those generated during transcription. Because of these properties, Z-DNA has been proposed to play roles in chromatin organization and gene regulation.
-[[File:ChromatinFibers.png|thumb|left|240x240px|Four proposed structures of the 30&nbsp;nm chromatin filament for DNA repeat length per nucleosomes ranging from 177 to 207 bp.
+Local DNA sequence composition and structural flexibility influence how DNA interacts with histone proteins and other chromatin-associated factors. For example, sequences enriched in adenine and thymine can bend more easily, affecting nucleosome positioning along the genome.
-<br />
-Linker DNA in yellow and nucleosomal DNA in pink.]]
-The existing models commonly accept that the nucleosomes lie perpendicular to the axis of the fibre, with linker histones arranged internally.
-A stable 30&nbsp;nm fibre relies on the regular positioning of nucleosomes along DNA. Linker DNA is relatively resistant to bending and rotation. This makes the length of linker DNA critical to the stability of the fibre, requiring nucleosomes to be separated by lengths that permit rotation and folding into the required orientation without excessive stress to the DNA.
-In this view, different lengths of the linker DNA should produce different folding topologies of the chromatin fiber. Recent theoretical work, based on electron-microscopy images<ref>
-{{cite journal
-|title=EM measurements define the dimensions of the "30-nm" chromatin fiber: Evidence for a compact, interdigitated structure
-|author1=Robinson DJ |author2=Fairall L |author3=Huynh VA |author4=Rhodes D. |journal=[[Proceedings of the National Academy of Sciences of the United States of America]]
-|date=April 2006
-|volume=103
-|issue=17
-|pages=6506–11
-|pmid=16617109
-|doi=10.1073/pnas.0601212103
-|pmc=1436021|bibcode=2006PNAS..103.6506R|doi-access=free }}
-</ref>
-of reconstituted fibers supports this view.<ref>
-{{cite journal
-|title= An All-Atom Model of the Chromatin Fiber Containing Linker Histones Reveals a Versatile Structure Tuned by the Nucleosomal Repeat Length
-|vauthors = Wong H, Victor JM, Mozziconacci J
-|journal= [[PLoS ONE]]
-|date= September 2007
-|volume= 2
-|issue= 9
-|pmid= 17849006 | doi = 10.1371/journal.pone.0000877
-|pages= e877
-|pmc= 1963316
-|editor1-last=Chen
-|editor1-first=Pu
-|bibcode= 2007PLoSO...2..877W
-|doi-access = free
-}} {{open access}}
-</ref>
-===DNA loops===
+== Chromatin during the cell cycle ==
-[[File:Emerging_Evidence_of_Chromosome_Folding_by_Loop_Extrusion_Supplemental_Movie_1.webm|thumb|Animated representation of the dynamic formation of chromatin loops through [[CTCF]] (red) and [[condensin]] rings (yellow)<ref name="Emerging Loop Extrusion"/>]]
-The beads-on-a-string chromatin structure has a tendency to form loops. These loops allow interactions between different regions of DNA by bringing them closer to each other, which increases the efficiency of gene interactions. This process is dynamic, with loops forming and disappearing. The loops are regulated by two main elements:<ref>{{cite journal|vauthors=Kadauke S, Blobel GA|date=2009|title=Chromatin loops in gene regulation|journal=Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms |volume=1789|issue=1|pages=17–25|doi=10.1016/j.bbagrm.2008.07.002|pmid=18675948 |pmc=2638769 }}</ref>
-* [[Cohesin]]s, [[protein complex]]es that generate loops by extrusion of the DNA fiber through the ring-like structure of the complex itself.<ref name="Emerging Loop Extrusion"/><ref>{{Cite journal |last=Davidson |first=Iain F. |last2=Bauer |first2=Benedikt |last3=Goetz |first3=Daniela |last4=Tang |first4=Wen |last5=Wutz |first5=Gordana |last6=Peters |first6=Jan-Michael |date=2019-12-13 |title=DNA loop extrusion by human cohesin |url=https://www.science.org/doi/10.1126/science.aaz3418 |journal=Science |language=en |volume=366 |issue=6471 |pages=1338–1345 |doi=10.1126/science.aaz3418 |issn=0036-8075|url-access=subscription }}</ref>
-* [[CTCF]], a [[transcription factor]] that limits the frontier of the DNA loop. To stop the growth of a loop, two CTCF molecules must be positioned in opposite directions to block the movement of the cohesin ring (''see video'').<ref name="Emerging Loop Extrusion">{{cite journal|vauthors=Fudenberg G, Abdennur N, Imakaev M, Goloborodko A, Mirny LA|title=Emerging Evidence of Chromosome Folding by Loop Extrusion|journal=Cold Spring Harbor Symposia on Quantitative Biology|date=2017|volume=82|pages=45–55|doi=10.1101/sqb.2017.82.034710|pmid=29728444|pmc=6512960}}</ref><ref>{{Cite journal |last=Busslinger |first=Georg A. |last2=Stocsits |first2=Roman R. |last3=van der Lelij |first3=Petra |last4=Axelsson |first4=Elin |last5=Tedeschi |first5=Antonio |last6=Galjart |first6=Niels |last7=Peters |first7=Jan-Michael |date=April 2017 |title=Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl |url=https://www.nature.com/articles/nature22063 |journal=Nature |language=en |volume=544 |issue=7651 |pages=503–507 |doi=10.1038/nature22063 |issn=0028-0836 |pmc=6080695 |pmid=28424523}}</ref>
-There are many other elements involved. For example, [[Jpx (gene)|Jpx]] regulates the binding sites of CTCF molecules along the DNA fiber.<ref>{{cite journal|vauthors=Oh HJ, Aguilar R, Kesner B, Lee HG, Kriz AJ, Chu HP, Lee JT|title=Jpx RNA regulates CTCF anchor site selection and formation of chromosome loops|journal=Cell|volume=184|issue=25|date=2021|pages=6157–6173|issn=0092-8674|doi=10.1016/j.cell.2021.11.012|pmid=34856126 |pmc=8671370 }}</ref>
 ===Spatial organization of chromatin in the cell nucleus===
 <!--- Too speculative for an article: "[[File:Nucleus & Chromatin Territorial Structure.jpg|thumb|200px|left|'''Fig. 4:''' Hypothetical Model of the Territorial Organization of Chromatin in the Cell Nucleus. The diagram (Fig. 4) represents a model of a cell (gray oval) with a nucleus (dark gray oval). Two chromosomes are shown as chromatin fibers (yellow and red lines). Proteins are represented as small ovals. Note the association of the chromatin components with the nuclear membrane. Chromosomes are territorially interlinked by chromatin protein complexes (scaffold proteins see above).]]" --->
-The spatial arrangement of the chromatin within the nucleus is not random - specific regions of the chromatin can be found in certain territories. Territories are, for example, the [[Topologically associating domain#Lamina-associated domains|lamina-associated domains]] (LADs), and the [[topologically associating domain]]s (TADs), which are bound together by protein complexes.<ref name="pmid24804566">{{cite journal |vauthors=Nicodemi M, Pombo A |title=Models of chromosome structure |journal=Curr. Opin. Cell Biol. |volume=28 |pages=90–5 |date=June 2014 |pmid=24804566 |doi=10.1016/j.ceb.2014.04.004 |url=http://edoc.mdc-berlin.de/14021/1/14021oa.pdf |archive-url=https://web.archive.org/web/20170921231635/http://edoc.mdc-berlin.de/14021/1/14021oa.pdf |archive-date=2017-09-21 |url-status=live}}</ref> Currently, polymer models such as the Strings & Binders Switch (SBS) model<ref name="pmid18493085">{{cite journal |vauthors=Nicodemi M, Panning B, Prisco A |title=A thermodynamic switch for chromosome colocalization |journal=Genetics |volume=179 |issue=1 |pages=717–21 |date=May 2008 |pmid=18493085 |pmc=2390650 |doi=10.1534/genetics.107.083154 |arxiv=0809.4788 }}</ref> and the Dynamic Loop (DL) model<ref name="pmid20811620">{{cite journal |vauthors=Bohn M, Heermann DW |title=Diffusion-driven looping provides a consistent framework for chromatin organization |journal=PLOS ONE |volume=5 |issue=8 |pages=e12218 |year=2010 |pmid=20811620 |pmc=2928267 |doi=10.1371/journal.pone.0012218 |bibcode=2010PLoSO...512218B |doi-access=free }}</ref> are used to describe the folding of chromatin within the nucleus. The arrangement of chromatin within the nucleus may also play a role in nuclear stress and restoring nuclear membrane deformation by mechanical stress. When chromatin is condensed, the nucleus becomes more rigid. When chromatin is decondensed, the nucleus becomes more elastic with less [[force]] exerted on the inner nuclear membrane. This observation sheds light on other possible cellular functions of chromatin organization outside of genomic regulation.<ref name="doi.org"/>
+The spatial arrangement of the chromatin within the nucleus is not random - specific regions of the chromatin can be found in certain territories. Territories are, for example, the [[Topologically associating domain#Lamina-associated domains|lamina-associated domains]] (LADs), and the [[topologically associating domain]]s (TADs), which are bound together by protein complexes.<ref name="pmid24804566">{{cite journal |vauthors=Nicodemi M, Pombo A |title=Models of chromosome structure |journal=Curr. Opin. Cell Biol. |volume=28 |pages=90–5 |date=June 2014 |pmid=24804566 |doi=10.1016/j.ceb.2014.04.004 |url=http://edoc.mdc-berlin.de/14021/1/14021oa.pdf |archive-url=https://web.archive.org/web/20170921231635/http://edoc.mdc-berlin.de/14021/1/14021oa.pdf |archive-date=2017-09-21 |url-status=live}}</ref> Polymer physics approaches have been widely used to model chromatin folding and genome organization. In particular, mechanisms such as [[loop extrusion]], mediated by protein complexes including cohesin, have been proposed to explain the formation of chromatin loops and domain boundaries observed in chromosome conformation capture experiments.
 ===Cell-cycle dependent structural organization===
@@ Line 128: / Line 99: @@
 # '''Interphase''': The structure of chromatin during [[interphase]] of [[mitosis]] is optimized to allow simple access of [[transcription (genetics)|transcription]] and [[DNA repair]] factors to the DNA while compacting the DNA into the [[nucleus (cell)|nucleus]]. The structure varies depending on the access required to the DNA. [[Genes]] that require regular access by [[RNA polymerase]] require the looser structure provided by euchromatin.
-# '''Metaphase''': The [[metaphase]] structure of chromatin differs vastly to that of [[interphase]]. It is optimised for physical strength{{Citation needed|date=July 2017}} and manageability, forming the classic [[chromosome]] structure seen in [[karyotype]]s. The structure of the condensed chromatin is thought to be loops of 30&nbsp;nm fibre to a central [[chromosome scaffold|scaffold]] of proteins. It is, however, not well-characterised. '''[[Chromosome scaffold]]s''' play an important role to hold the chromatin into compact chromosomes. Loops of 30&nbsp;nm structure further condense with scaffold, into higher order structures.<ref>{{cite book |last1=Lodish |first1=Harvey F. |title=Molecular Cell Biology |date=2016 |publisher=W. H. Freeman and Company |location=New York |isbn=978-1-4641-8339-3 |page=339 |edition=8th}}</ref> Chromosome scaffolds are made of proteins including [[condensin]], [[Type II topoisomerase#Type IIA|type IIA topoisomerase]]  and kinesin family member 4 (KIF4).<ref>{{cite journal |last1=Poonperm |first1=R |last2=Takata |first2=H |last3=Hamano |first3=T |last4=Matsuda |first4=A |last5=Uchiyama |first5=S |last6=Hiraoka |first6=Y |last7=Fukui |first7=K |title=Chromosome Scaffold is a Double-Stranded Assembly of Scaffold Proteins. |journal=Scientific Reports |date=1 July 2015 |volume=5 |pages=11916 |doi=10.1038/srep11916 |pmid=26132639 |pmc=4487240|bibcode=2015NatSR...511916P }}</ref> The physical strength of chromatin is vital for this stage of division to prevent shear damage to the DNA as the daughter chromosomes are separated. To maximise strength the composition of the chromatin changes as it approaches the centromere, primarily through alternative histone H1 analogues. During mitosis, although most of the chromatin is tightly compacted, there are small regions that are not as tightly compacted. These regions often correspond to promoter regions of genes that were active in that cell type prior to chromatin formation. The lack of compaction of these regions is called [[bookmarking]], which is an [[epigenetic]] mechanism believed to be important for transmitting to daughter cells the "memory" of which genes were active prior to entry into mitosis.<ref>{{cite journal |vauthors=Xing H, Vanderford NL, Sarge KD |title=The TBP-PP2A mitotic complex bookmarks genes by preventing condensin action |journal=Nat. Cell Biol. |volume=10 |issue=11 |pages=1318–23 |date=November 2008 |pmid=18931662 |pmc=2577711 |doi=10.1038/ncb1790 }}</ref> This [[bookmarking]] mechanism is needed to help transmit this memory because transcription ceases during [[mitosis]].
+# '''Metaphase''': The [[metaphase]] structure of chromatin differs vastly to that of [[interphase]]. It is optimised for physical strength{{Citation needed|date=July 2017}} and manageability, forming the classic [[chromosome]] structure seen in [[karyotype]]s. The structure of the condensed chromatin is thought to be loops of 30&nbsp;nm fibre to a central [[chromosome scaffold|scaffold]] of proteins. It is, however, not well-characterised. '''[[Chromosome scaffold]]s''' play an important role to hold the chromatin into compact chromosomes. Loops of 30&nbsp;nm structure further condense with scaffold, into higher order structures.<ref>{{cite book |last1=Lodish |first1=Harvey F. |title=Molecular Cell Biology |date=2016 |publisher=W. H. Freeman and Company |location=New York |isbn=978-1-4641-8339-3 |page=339 |edition=8th}}</ref> Chromosome scaffolds are made of proteins including [[condensin]], [[Type II topoisomerase#Type IIA|type IIA topoisomerase]]  and kinesin family member 4 (KIF4).<ref>{{cite journal |last1=Poonperm |first1=R |last2=Takata |first2=H |last3=Hamano |first3=T |last4=Matsuda |first4=A |last5=Uchiyama |first5=S |last6=Hiraoka |first6=Y |last7=Fukui |first7=K |title=Chromosome Scaffold is a Double-Stranded Assembly of Scaffold Proteins. |journal=Scientific Reports |date=1 July 2015 |volume=5 |article-number=11916 |doi=10.1038/srep11916 |pmid=26132639 |pmc=4487240|bibcode=2015NatSR...511916P }}</ref> The physical strength of chromatin is vital for this stage of division to prevent shear damage to the DNA as the daughter chromosomes are separated. To maximise strength the composition of the chromatin changes as it approaches the centromere, primarily through alternative histone H1 analogues. During mitosis, although most of the chromatin is tightly compacted, there are small regions that are not as tightly compacted. These regions often correspond to promoter regions of genes that were active in that cell type prior to chromatin formation. The lack of compaction of these regions is called [[bookmarking]], which is an [[epigenetic]] mechanism believed to be important for transmitting to daughter cells the "memory" of which genes were active prior to entry into mitosis.<ref>{{cite journal |vauthors=Xing H, Vanderford NL, Sarge KD |title=The TBP-PP2A mitotic complex bookmarks genes by preventing condensin action |journal=Nat. Cell Biol. |volume=10 |issue=11 |pages=1318–23 |date=November 2008 |pmid=18931662 |pmc=2577711 |doi=10.1038/ncb1790 }}</ref> This [[bookmarking]] mechanism is needed to help transmit this memory because transcription ceases during [[mitosis]].
-==Chromatin and bursts of transcription==
-Chromatin and its interaction with enzymes has been researched, and a conclusion being made is that it is relevant and an important factor in gene expression. Vincent G. Allfrey, a professor at Rockefeller University, stated that RNA synthesis is related to histone acetylation.<ref name="pmid14172992">{{cite journal |vauthors=Allfrey VG, Faulkner R, Mirsky AE |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=51 |issue= 5|pages=786–94 |date=May 1964 |pmid=14172992 |pmc=300163 |doi= 10.1073/pnas.51.5.786|bibcode=1964PNAS...51..786A |title=Acetylation and Methylation of Histones and Their Possible Role in the Regulation of RNA Synthesis |doi-access=free }}</ref> The lysine amino acid attached to the end of the histones is positively charged. The acetylation of these tails would make the chromatin ends neutral, allowing for DNA access.
-When the chromatin decondenses, the DNA is open to entry of molecular machinery. Fluctuations between open and closed chromatin may contribute to the discontinuity of transcription, or [[transcriptional bursting]].  Other factors are probably involved, such as the association and dissociation of transcription factor complexes with chromatin. Specifically, RNA polymerase and transcriptional proteins have been shown to congregate into droplets via phase separation, and recent studies have suggested that 10&nbsp;nm chromatin demonstrates liquid-like behavior increasing the targetability of genomic DNA.<ref>Maeshima, K., Ide, S., Hibino, K., & Sasai, M. (2016). Liquid-like behavior of chromatin. ''Current opinion in genetics & development, 37,'' 36–45. https://doi.org/10.1016/j.gde.2015.11.006</ref> The interactions between linker histones and disordered tail regions act as an electrostatic glue organizing large-scale chromatin into a dynamic, liquid-like domain. Decreased chromatin compaction comes with increased chromatin mobility and easier transcriptional access to DNA.<ref name="doi.org"/> The phenomenon, as opposed to simple probabilistic models of transcription, can account for the high variability in gene expression occurring between cells in isogenic populations.<ref name="pmid22944281">{{cite journal |vauthors=Kaochar S, Tu BP |title=Gatekeepers of chromatin: Small metabolites elicit big changes in gene expression |journal=Trends Biochem. Sci. |volume=37 |issue=11 |pages=477–83 |date=November 2012 |pmid=22944281 |pmc=3482309 |doi=10.1016/j.tibs.2012.07.008 }}</ref>
+== Specialized chromatin states ==
-===Alternative chromatin organizations===
+=== Sperm chromatin ===
 During metazoan [[spermiogenesis]], the [[spermatid]]'s chromatin is remodeled into a more spaced-packaged, widened, almost crystal-like structure. This process is associated with the cessation of [[transcription (genetics)|transcription]] and involves [[cell nucleus|nuclear]] protein exchange. The histones are mostly displaced, and replaced by [[protamine]]s (small, [[arginine]]-rich proteins).<ref name="pmid23213436">{{cite journal |vauthors=De Vries M, Ramos L, Housein Z, De Boer P |title=Chromatin remodelling initiation during human spermiogenesis |journal=Biol Open |volume=1 |issue=5 |pages=446–57 |date=May 2012 |pmid=23213436 |pmc=3507207 |doi=10.1242/bio.2012844 }}</ref> It is proposed that in yeast, regions devoid of histones become very fragile after transcription; HMO1, an [[HMG-box]] protein, helps in stabilizing nucleosomes-free chromatin.<ref name="pmid25063301">{{cite journal | vauthors = Murugesapillai D, McCauley MJ, Huo R, Nelson Holte MH, Stepanyants A, Maher LJ, Israeloff NE, Williams MC | title = DNA bridging and looping by HMO1 provides a mechanism for stabilizing nucleosome-free chromatin | journal = Nucleic Acids Research | volume = 42 | issue = 14 | pages = 8996–9004 | date = August 2014 | pmid = 25063301 | pmc = 4132745 | doi = 10.1093/nar/gku635 }}</ref><ref name="pmid28303166">{{cite journal | vauthors = Murugesapillai D, McCauley MJ, Maher LJ, Williams MC | title = Single-molecule studies of high-mobility group B architectural DNA bending proteins | journal = Biophysical Reviews | volume = 9 | issue = 1 | pages = 17–40 | date = February 2017 | pmid = 28303166 | pmc = 5331113 | doi = 10.1007/s12551-016-0236-4 }}</ref>
@@ Line 142: / Line 109: @@
 ==Chromatin and DNA repair==
-A variety of internal and external agents can cause DNA damage in cells. Many factors influence how the repair route is selected, including the cell cycle phase and chromatin segment where the break occurred. In terms of initiating 5’ end DNA repair, the p53 binding protein 1 ([[TP53BP1|53BP1]]) and [[BRCA1]] are important protein components that influence double-strand break repair pathway selection. The 53BP1 complex attaches to chromatin near DNA breaks and activates downstream factors such as Rap1-Interacting Factor 1 ([[Telomere-associated protein RIF1|RIF1]]) and shieldin, which protects DNA ends against nucleolytic destruction. DNA damage process occurs within the condition of chromatin, and the constantly changing chromatin environment has a large effect on it.<ref>{{Cite journal |last1=Aleksandrov |first1=Radoslav |last2=Hristova |first2=Rossitsa |last3=Stoynov |first3=Stoyno |last4=Gospodinov |first4=Anastas |date=2020-08-07 |title=The Chromatin Response to Double-Strand DNA Breaks and Their Repair |journal=Cells |language=en |volume=9 |issue=8 |pages=1853 |doi=10.3390/cells9081853 |pmid=32784607 |pmc=7464352 |issn=2073-4409|doi-access=free }}</ref> Accessing and repairing the damaged cell of DNA, the genome condenses into chromatin and repairing it through modifying the histone residues. Through altering the chromatin structure, histones residues are adding chemical groups namely phosphate, acetyl and one or more methyl groups and these control the expressions of gene building by proteins to acquire DNA.<ref>{{Cite journal |last1=Miné-Hattab |first1=Judith |last2=Chiolo |first2=Irene |date=2020-08-27 |title=Complex Chromatin Motions for DNA Repair |journal=Frontiers in Genetics |volume=11 |pages=800 |doi=10.3389/fgene.2020.00800 |pmid=33061931 |pmc=7481375 |issn=1664-8021|doi-access=free }}</ref> Moreover, resynthesis of the delighted zone, DNA will be repaired by processing and restructuring the damaged bases. In order to maintain genomic integrity, "homologous recombination and classical non-homologous end joining process" has been followed by DNA to be repaired.<ref>{{Cite journal |last1=Lamm |first1=Noa |last2=Rogers |first2=Samuel |last3=Cesare |first3=Anthony J. |date=October 2021 |title=Chromatin mobility and relocation in DNA repair |journal=Trends in Cell Biology |volume=31 |issue=10 |pages=843–855 |doi=10.1016/j.tcb.2021.06.002 |pmid=34183232 |s2cid=235672793 |issn=0962-8924|doi-access=free }}</ref>
+A variety of internal and external agents can cause DNA damage in cells. Many factors influence how the repair route is selected, including the cell cycle phase and chromatin segment where the break occurred. In terms of initiating 5' end DNA repair, the p53 binding protein 1 ([[TP53BP1|53BP1]]) and [[BRCA1]] are important protein components that influence double-strand break repair pathway selection. The 53BP1 complex attaches to chromatin near DNA breaks and activates downstream factors such as Rap1-Interacting Factor 1 ([[Telomere-associated protein RIF1|RIF1]]) and shieldin, which protects DNA ends against nucleolytic destruction. DNA damage process occurs within the condition of chromatin, and the constantly changing chromatin environment has a large effect on it.<ref>{{Cite journal |last1=Aleksandrov |first1=Radoslav |last2=Hristova |first2=Rossitsa |last3=Stoynov |first3=Stoyno |last4=Gospodinov |first4=Anastas |date=2020-08-07 |title=The Chromatin Response to Double-Strand DNA Breaks and Their Repair |journal=Cells |language=en |volume=9 |issue=8 |page=1853 |doi=10.3390/cells9081853 |pmid=32784607 |pmc=7464352 |issn=2073-4409|doi-access=free }}</ref> Accessing and repairing the damaged cell of DNA, the genome condenses into chromatin and repairing it through modifying the histone residues. Through altering the chromatin structure, histones residues are adding chemical groups namely phosphate, acetyl and one or more methyl groups and these control the expressions of gene building by proteins to acquire DNA.<ref>{{Cite journal |last1=Miné-Hattab |first1=Judith |last2=Chiolo |first2=Irene |date=2020-08-27 |title=Complex Chromatin Motions for DNA Repair |journal=Frontiers in Genetics |volume=11 |article-number=800 |doi=10.3389/fgene.2020.00800 |pmid=33061931 |pmc=7481375 |issn=1664-8021|doi-access=free }}</ref> Moreover, resynthesis of the delighted zone, DNA will be repaired by processing and restructuring the damaged bases. In order to maintain genomic integrity, "homologous recombination and classical non-homologous end joining process" has been followed by DNA to be repaired.<ref>{{Cite journal |last1=Lamm |first1=Noa |last2=Rogers |first2=Samuel |last3=Cesare |first3=Anthony J. |date=October 2021 |title=Chromatin mobility and relocation in DNA repair |journal=Trends in Cell Biology |volume=31 |issue=10 |pages=843–855 |doi=10.1016/j.tcb.2021.06.002 |pmid=34183232 |s2cid=235672793 |issn=0962-8924|doi-access=free }}</ref>
 The packaging of eukaryotic DNA into chromatin presents a barrier to all DNA-based processes that require recruitment of enzymes to their sites of action.<ref>{{Citation |last1=Trotter |first1=Kevin W. |title=Assaying Chromatin Structure and Remodeling by Restriction Enzyme Accessibility |date=2012 |work=Chromatin Remodeling |volume=833 |pages=89–102 |editor-last=Morse |editor-first=Randall H. |place=Totowa, NJ |publisher=Humana Press |doi=10.1007/978-1-61779-477-3_6 |pmid=22183589 |pmc=3607496 |isbn=978-1-61779-476-6 |last2=Archer |first2=Trevor K.|series=Methods in Molecular Biology }}</ref> To allow the critical cellular process of DNA repair, the chromatin must be remodeled.  In eukaryotes, [[ATP-dependent chromatin remodeling]] complexes and [[histone-modifying enzymes]] are two predominant factors employed to accomplish this remodeling process.<ref name="Liu">{{cite journal |vauthors=Liu B, Yip RK, Zhou Z |title=Chromatin remodeling, DNA damage repair and aging |journal=Curr. Genomics |volume=13 |issue=7 |pages=533–47 |year=2012 |pmid=23633913 |pmc=3468886 |doi=10.2174/138920212803251373 }}</ref>
@@ Line 152: / Line 119: @@
 After undergoing relaxation subsequent to DNA damage, followed by DNA repair, chromatin recovers to a compaction state close to its pre-damage level after about 20 min.<ref name=Sellou />
-==Methods to investigate chromatin==
+==Methods to study chromatin==
 [[File:Heterochromatic versus euchromatic nuclei.jpg|thumb|Microscopy of heterochromatic versus euchromatic nuclei (H&E stain).]]
 [[File:Well-differentiated neuroendocrine tumor with salt-and-pepper chromatin.png|thumb|Granular "[[salt-and-pepper chromatin]]", seen on H&E, Pap stain and comparison to actual salt and pepper. Its finding on microscopy indicates mainly [[medullary thyroid carcinoma]], [[neuroendocrine tumour]]s<ref>{{cite journal  |vauthors=Van Buren G, Rashid A, Yang AD, etal |title=The development and characterization of a human midgut carcinoid cell line |journal=Clin. Cancer Res. |volume=13 |issue=16 |pages=4704–12 |date=August 2007 |pmid=17699847 |doi=10.1158/1078-0432.CCR-06-2723 |doi-access=free }}</ref> or [[pheochromocytoma]].<ref>{{cite journal |vauthors=Shidham VB, Galindo LM |title=Pheochromocytoma. Cytologic findings on intraoperative scrape smears in five cases |journal=Acta Cytol. |volume=43 |issue=2 |pages=207–13 |year=1999 |pmid=10097711 |doi= 10.1159/000330978|s2cid=232277473 }}</ref>]]
 [[File:Human karyotype with bands and sub-bands.png|thumb|Schematic [[karyotype|karyogram]] of a [[human]], showing an overview of the [[human genome]] using [[G banding]], which is a method that includes [[Giemsa stain]]ing, wherein the lighter staining regions are generally more [[euchromatic]] (and more [[Transcription (biology)|transcriptionally]] active), whereas darker regions generally are more [[heterochromatic]].{{further|Karyotype}}]]
-# '''[[ChIP-sequencing|ChIP-seq]]''' (Chromatin immunoprecipitation sequencing) is recognized as the vastly utilized chromatin identification method it has been using the antibodies that actively selected, identify and combine with proteins including "histones, histone restructuring, transaction factors and cofactors". This has been providing data about the state of chromatin and the transaction of a gene by trimming "oligonucleotides" that are unbound.<ref>{{Citation |last1=Small |first1=Eliza C. |title=Chromatin Immunoprecipitation (ChIP) to Study DNA–Protein Interactions |date=2021 |url=http://link.springer.com/10.1007/978-1-0716-1186-9_20 |work=Proteomic Profiling |volume=2261 |pages=323–343 |editor-last=Posch |editor-first=Anton |place=New York, NY |publisher=Springer US |language=en |doi=10.1007/978-1-0716-1186-9_20 |pmid=33420999 |isbn=978-1-0716-1185-2 |access-date=2022-10-24 |last2=Maryanski |first2=Danielle N. |last3=Rodriguez |first3=Keli L. |last4=Harvey |first4=Kevin J. |last5=Keogh |first5=Michael-C. |last6=Johnstone |first6=Andrea L.|series=Methods in Molecular Biology |s2cid=231304041 |url-access=subscription }}</ref> Chromatin immunoprecipitation sequencing aimed against different [[histone modification]]s, can be used to identify chromatin states throughout the genome. Different modifications have been linked to various states of chromatin.<ref>{{cite journal |last1=Rossi |first1=M.J |last2=Kuntala |first2=P.K |last3=Lai |first3=W.K.M |display-authors=etal |title=A high-resolution protein architecture of the budding yeast genome |journal=Nature |date=10 March 2021 |volume=592 |issue=7853 |pages=309–314 |doi=10.1038/s41586-021-03314-8 |pmid=33692541|pmc=8035251 |bibcode=2021Natur.592..309R }}</ref>
+# '''[[ChIP-sequencing|ChIP-seq]]''' (Chromatin immunoprecipitation sequencing) is recognized as the vastly utilized chromatin identification method it has been using the antibodies that actively select, identify and combine with proteins including "histones, histone restructuring, transcription factors and cofactors". This has been providing data about the state of chromatin and the transcription of a gene by trimming "oligonucleotides" that are unbound.<ref>{{Citation |last1=Small |first1=Eliza C. |title=Chromatin Immunoprecipitation (ChIP) to Study DNA–Protein Interactions |date=2021 |url=http://link.springer.com/10.1007/978-1-0716-1186-9_20 |work=Proteomic Profiling |volume=2261 |pages=323–343 |editor-last=Posch |editor-first=Anton |place=New York, NY |publisher=Springer US |language=en |doi=10.1007/978-1-0716-1186-9_20 |pmid=33420999 |isbn=978-1-0716-1185-2 |access-date=2022-10-24 |last2=Maryanski |first2=Danielle N. |last3=Rodriguez |first3=Keli L. |last4=Harvey |first4=Kevin J. |last5=Keogh |first5=Michael-C. |last6=Johnstone |first6=Andrea L.|series=Methods in Molecular Biology |s2cid=231304041 |url-access=subscription }}</ref> Chromatin immunoprecipitation sequencing aimed against different [[histone modification]]s, can be used to identify chromatin states throughout the genome. Different modifications have been linked to various states of chromatin.<ref>{{cite journal |last1=Rossi |first1=M.J |last2=Kuntala |first2=P.K |last3=Lai |first3=W.K.M |display-authors=etal |title=A high-resolution protein architecture of the budding yeast genome |journal=Nature |date=10 March 2021 |volume=592 |issue=7853 |pages=309–314 |doi=10.1038/s41586-021-03314-8 |pmid=33692541|pmc=8035251 |bibcode=2021Natur.592..309R }}</ref>
 # '''[[DNase-Seq|DNase-seq]]''' (DNase I hypersensitive sites Sequencing) uses the sensitivity of accessible regions in the genome to the [[DNase I]] enzyme to map open or accessible regions in the genome.
 # '''[[FAIRE-Seq|FAIRE-seq]]''' ([[Formaldehyde]]-Assisted Isolation of Regulatory Elements sequencing) uses the chemical properties of protein-bound DNA in a two-phase separation method to extract  nucleosome depleted regions from the genome.<ref>{{Cite journal
@@ Line 242: / Line 209: @@
 | journal = Nature Communications
 | volume = 7
-| pages = 11485
+| article-number = 11485
 | doi = 10.1038/ncomms11485
 | pmc = 4859066
@@ Line 249: / Line 216: @@
 }}</ref>
-==Chromatin and knots==
+== Physical and topological properties ==
+=== Chromatin knots ===
 It has been a puzzle how decondensed interphase chromosomes remain essentially unknotted. The natural expectation is that in the presence of type II DNA topoisomerases that permit passages of double-stranded DNA regions through each other, all chromosomes should reach the state of topological equilibrium. The topological equilibrium in highly crowded interphase chromosomes forming chromosome territories would result in formation of highly knotted chromatin fibres. However, Chromosome Conformation Capture (3C) methods revealed that the decay of contacts with the genomic distance in interphase chromosomes is practically the same as in the crumpled globule state that is formed when long polymers condense without formation of any knots. To remove knots from highly crowded chromatin, one would need an active process that should not only provide the energy to move the system from the state of topological equilibrium but also guide topoisomerase-mediated passages in such a way that knots would be efficiently unknotted instead of making the knots even more complex. It has been shown that the process of chromatin-loop extrusion is ideally suited to actively unknot chromatin fibres in interphase chromosomes.<ref name="Racko 2018">{{cite journal |vauthors=Racko D, Benedetti F, Goundaroulis D, Stasiak A|title=Chromatin Loop Extrusion and Chromatin Unknotting |journal=Polymers |volume=10 |issue=10 |pages=1126–1137 |year=2018 |doi= 10.3390/polym10101126|pmid=30961051 |pmc=6403842 |doi-access=free }}</ref>
-==Chromatin: alternative definitions==
-The term, introduced by [[Walther Flemming]], has multiple meanings:
-# '''Simple and concise definition:''' Chromatin is a macromolecular complex of a DNA macromolecule and protein macromolecules (and RNA). The proteins package and arrange the DNA and control its functions within the cell nucleus.
-# '''A biochemists' operational definition:''' Chromatin is the DNA/protein/RNA complex extracted from eukaryotic lysed interphase nuclei. Just which of the multitudinous substances present in a nucleus will constitute a part of the extracted material partly depends on the technique each researcher uses. Furthermore, the composition and properties of chromatin vary from one cell type to another, during the development of a specific cell type, and at different stages in the cell cycle.
-# '''The ''DNA + histone = chromatin'' definition:''' The DNA double helix in the cell nucleus is packaged by special proteins termed histones. The formed protein/DNA complex is called chromatin. The basic structural unit of chromatin is the nucleosome.
-The first definition allows for "chromatins" to be defined in other domains of life like bacteria and archaea, using any DNA-binding proteins that [[DNA condensation|condenses the molecule]]. These proteins are usually referred to [[Nucleoid#Nucleoid-associated proteins (NAPs)|nucleoid-associated proteins]] (NAPs); examples include AsnC/LrpC with HU. In addition, some archaea do produce nucleosomes from proteins homologous to eukaryotic histones.<ref>{{cite journal |last1=Luijsterburg |first1=Martijn S. |last2=White |first2=Malcolm F. |last3=van Driel |first3=Roel |last4=Dame |first4=Remus Th. |title=The Major Architects of Chromatin: Architectural Proteins in Bacteria, Archaea and Eukaryotes |journal=Critical Reviews in Biochemistry and Molecular Biology |date=8 January 2009 |volume=43 |issue=6 |pages=393–418 |doi=10.1080/10409230802528488|pmid=19037758 |s2cid=85874882 }}</ref>
-Chromatin Remodeling:
-Chromatin remodeling can result from covalent modification of histones that physically remodel, move or remove nucleosomes.<ref>{{Cite web |title=Chromatin remodelling - Latest research and news {{!}} Nature |url=https://www.nature.com/subjects/chromatin-remodelling |access-date=2023-01-07 |website=www.nature.com}}</ref> Studies of Sanosaka et al. 2022, says that Chromatin remodeler CHD7 regulate cell type-specific gene expression in human neural crest cells.<ref>{{Cite journal |last1=Sanosaka |first1=Tsukasa |last2=Okuno |first2=Hironobu |last3=Mizota |first3=Noriko |last4=Andoh-Noda |first4=Tomoko |last5=Sato |first5=Miki |last6=Tomooka |first6=Ryo |last7=Banno |first7=Satoe |last8=Kohyama |first8=Jun |last9=Okano |first9=Hideyuki |date=2022-12-31 |title=Chromatin remodeler CHD7 targets active enhancer region to regulate cell type-specific gene expression in human neural crest cells |journal=Scientific Reports |language=en |volume=12 |issue=1 |pages=22648 |doi=10.1038/s41598-022-27293-6 |pmid=36587182 |pmc=9805427 |bibcode=2022NatSR..1222648S |issn=2045-2322}}</ref>
 ==See also==
@@ Line 271: / Line 226: @@
 * [[Active chromatin sequence]]
 * [[Chromatid]]
+* [[Chromosome]]
 * [[ENCODE]] database
 * [[Epigenetics]]
@@ Line 297: / Line 253: @@
 * {{cite journal | last1 = Gerasimova | first1 = T. I. | last2 = Byrd | first2 = K. | last3 = Corces | first3 = V. G. | year = 2000 | title = A chromatin insulator determines the nuclear localization of DNA [In Process Citation] | journal = Mol Cell | volume = 6 | issue = 5| pages = 1025–35 | doi=10.1016/s1097-2765(00)00101-5| pmid = 11106742 | doi-access = free }}
 * {{cite journal | last1 = Ha | first1 = S. C. | last2 = Lowenhaupt | first2 = K. | last3 = Rich | first3 = A. | last4 = Kim | first4 = Y. G. | last5 = Kim | first5 = K. K. | year = 2005 | title = Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases | journal = Nature | volume = 437 | issue = 7062| pages = 1183–6 | doi=10.1038/nature04088 | pmid=16237447| bibcode = 2005Natur.437.1183H | s2cid = 2539819 }}
+*Morse, RH, 2024, Chromatin: Structure, Function, and History. Academic Press. ISBN 978-0-12-814809-9.
 * Pollard, T., and W. Earnshaw. 2002. Cell Biology. Saunders.
 * Saumweber, H. 1987. Arrangement of Chromosomes in Interphase Cell Nuclei, p.&nbsp;223-234. In W. Hennig (ed.), Structure and Function of Eucaryotic Chromosomes, vol. 14. Springer-Verlag, Berlin, Heidelberg.

Chromatin: Difference between revisions

Latest revision as of 21:53, 19 May 2026

Basic chromatin structure

Nucleosomes

Historical 30-nm fiber model

Three-dimensional genome organization

Chromatin loops

TADs

Chromatin compartments

Chromosome territories

Chromatin dynamics and regulation

Histone modifications

Chromatin remodeling

Transcriptional bursting

Structure of DNA

Chromatin during the cell cycle

Spatial organization of chromatin in the cell nucleus

Cell-cycle dependent structural organization

Specialized chromatin states

Sperm chromatin

Chromatin and DNA repair

Methods to study chromatin

Physical and topological properties

Chromatin knots

See also

Notes

References

Additional sources

External links

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