Array ( [0] => {{short description|Complex of DNA and protein in eukaryotic cells}} [1] => [[File:Chromatin Structures.png|thumb|360px|The major structures in DNA compaction: [[DNA]], the [[nucleosome]], the 10 nm [[beads on a string]] chromatin fibre and the [[metaphase]] [[chromosome]].]] [2] => [3] => '''Chromatin''' is a complex of [[DNA]] and [[protein]] found in [[eukaryote|eukaryotic]] cells.{{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}} 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. [4] => [5] => 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.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 In general, there are three levels of chromatin organization: [6] => [7] => # DNA wraps around histone proteins, forming [[nucleosome]]s and the so-called [[beads on a string]] structure ([[euchromatin]]). [8] => # 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.{{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}}}} [9] => # Higher-level [[DNA supercoiling]] of the 30 nm fiber produces the [[metaphase]] chromosome (during mitosis and meiosis). [10] => [11] => 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). [12] => [13] => 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]]. [14] => {{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= }} [[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]]. [15] => [16] => ==Dynamic chromatin structure and hierarchy== [17] => [[File:Basic units of chromatin structure.svg|thumb|Basic units of chromatin structure]] [18] => [[File:Chromosome en.svg|thumb|the structure of chromatin within a chromosome]] [19] => 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. 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 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.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 [20] => [21] => {{cite journal [22] => |title= A bivalent chromatin structure marks key developmental genes in embryonic stem cells [23] => |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 [24] => |journal= [[Cell (journal)|Cell]] [25] => |date= April 2006 [26] => |volume= 125 [27] => |issue= 2 [28] => |pages= 315–26 [29] => |pmid= 16630819 [30] => |issn= 0092-8674 [31] => |doi= 10.1016/j.cell.2006.02.041|s2cid = 9993008 [32] => |doi-access= free [33] => }} [34] => [35] => [36] => [[Polycomb-group proteins]] play a role in regulating genes through modulation of chromatin structure.{{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}} [37] => [38] => 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]]. [39] => [40] => ===Structure of DNA=== [41] => [[File:A-DNA, B-DNA and Z-DNA.png|thumb|left|300px|The structures of A-, B-, and Z-DNA.]] [42] => {{main|Mechanical properties of DNA|Z-DNA}} [43] => 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. [44] => [45] => 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”''.{{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 }} 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. [46] => [47] => {{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}} [61] => [62] => ===Nucleosomes and beads-on-a-string=== [63] => {{Main article|Nucleosome|Chromatosome|Histone}} [64] => [[File:Nucleosome 1KX5 2.png|thumb|left|150px|A cartoon representation of the nucleosome structure. From {{PDB|1KX5}}.]] [65] => The basic repeat element of chromatin is the nucleosome, interconnected by sections of [[linker DNA]], a far shorter arrangement than pure DNA in solution. [66] => [67] => 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 10 nm [[beads on a string]] fibre. [68] => [69] => 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]].) [70] => [71] => ===30-nm chromatin fiber in mitosis=== [72] => [[File:30nm Chromatin Structures.png|thumb|right|200px|Two proposed structures of the 30 nm chromatin filament.
Left: 1 start helix "solenoid" structure.
Right: 2 start loose helix structure.
Note: the histones are omitted in this diagram - only the DNA is shown.]] [73] => With addition of H1, during [[mitosis]] the [[Beads on a string|beads-on-a-string structure]] can coil into a 30 nm-diameter helical structure known as the 30 nm fibre or filament. The precise structure of the chromatin fiber in the cell is not known in detail.{{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}} [74] => [75] => 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 nm fiber is highly dynamic such that it unfolds into a 10 nm fiber beads-on-a-string structure when transversed by an RNA polymerase engaged in transcription. [76] => [77] => [[File:ChromatinFibers.png|thumb|left|250px|Four proposed structures of the 30 nm chromatin filament for DNA repeat length per nucleosomes ranging from 177 to 207 bp. [78] =>
[79] => Linker DNA in yellow and nucleosomal DNA in pink.]] [80] => The existing models commonly accept that the nucleosomes lie perpendicular to the axis of the fibre, with linker histones arranged internally. [81] => A stable 30 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. [82] => 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 [83] => {{cite journal [84] => |title=EM measurements define the dimensions of the "30-nm" chromatin fiber: Evidence for a compact, interdigitated structure [85] => |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]] [86] => |date=April 2006 [87] => |volume=103 [88] => |issue=17 [89] => |pages=6506–11 [90] => |pmid=16617109 [91] => |doi=10.1073/pnas.0601212103 [92] => |pmc=1436021|bibcode=2006PNAS..103.6506R|doi-access=free }} [93] => [94] => of reconstituted fibers supports this view. [95] => {{cite journal [96] => |title= An All-Atom Model of the Chromatin Fiber Containing Linker Histones Reveals a Versatile Structure Tuned by the Nucleosomal Repeat Length [97] => |vauthors = Wong H, Victor JM, Mozziconacci J [98] => |journal= [[PLoS ONE]] [99] => |date= September 2007 [100] => |volume= 2 [101] => |issue= 9 [102] => |pmid= 17849006 | doi = 10.1371/journal.pone.0000877 [103] => |pages= e877 [104] => |pmc= 1963316 [105] => |editor1-last=Chen [106] => |editor1-first=Pu [107] => |bibcode= 2007PLoSO...2..877W [108] => |doi-access = free [109] => }} {{open access}} [110] => [111] => ===DNA loops=== [112] => [[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)]] [113] => 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:{{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 }} [114] => * [[Cohesin]]s, [[protein complex]]es that generate loops by extrusion of the DNA fiber through the ring-like structure of the complex itself. [115] => * [[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'').{{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}} [116] => There are many other elements involved. For example, [[Jpx (gene)|Jpx]] regulates the binding sites of CTCF molecules along the DNA fiber.{{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 }} [117] => ===Spatial organization of chromatin in the cell nucleus=== [118] => [119] => [120] => 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.{{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}} Currently, polymer models such as the Strings & Binders Switch (SBS) model{{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 }} and the Dynamic Loop (DL) model{{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 }} 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. [121] => [122] => ===Cell-cycle dependent structural organization=== [123] => [[File:NHGRI human male karyotype.png|thumb|left|[[Karyogram]] of human male using [[Giemsa staining]], showing the classic [[metaphase]] chromatin structure.]] [124] => [[File:Condensation and resolution of human sister chromatids in early mitosis.svg|thumb|Condensation and resolution of human sister chromatids in early mitosis]] [125] => [126] => # '''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. [127] => # '''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 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 nm structure further condense with scaffold, into higher order structures.{{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}} Chromosome scaffolds are made of proteins including [[condensin]], [[Type II topoisomerase#Type IIA|type IIA topoisomerase]] and kinesin family member 4 (KIF4).{{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 }} 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.{{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 }} This [[bookmarking]] mechanism is needed to help transmit this memory because transcription ceases during [[mitosis]]. [128] => [129] => ==Chromatin and bursts of transcription== [130] => [131] => 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.{{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 }} 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. [132] => [133] => 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.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 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. 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.{{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 }} [134] => [135] => ===Alternative chromatin organizations=== [136] => [137] => 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).{{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 }} 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.{{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 }}{{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 }} [138] => [139] => ==Chromatin and DNA repair== [140] => [141] => 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.{{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 }} 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.{{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 }} 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.{{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 }} [142] => [143] => 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.{{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 }} 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.{{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 }} [144] => [145] => Chromatin relaxation occurs rapidly at the site of DNA damage.{{cite journal |vauthors=Sellou H, Lebeaupin T, Chapuis C, Smith R, Hegele A, Singh HR, Kozlowski M, Bultmann S, Ladurner AG, Timinszky G, Huet S |title=The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage |journal=Mol. Biol. Cell |volume=27 |issue=24 |pages=3791–3799 |year=2016 |pmid=27733626 |pmc=5170603 |doi=10.1091/mbc.E16-05-0269 }} 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.{{cite journal |vauthors=Haince JF, McDonald D, Rodrigue A, Déry U, Masson JY, Hendzel MJ, Poirier GG |title=PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites |journal=J. Biol. Chem. |volume=283 |issue=2 |pages=1197–208 |year=2008 |pmid=18025084 |doi=10.1074/jbc.M706734200 |doi-access=free }} Next the chromatin remodeler [[CHD1L|Alc1]] quickly attaches to the product of PARP1, and completes arrival at the DNA damage within 10 seconds of the damage. About half of the maximum chromatin relaxation, presumably due to action of Alc1, occurs by 10 seconds. This then allows recruitment of the DNA repair enzyme [[MRE11A|MRE11]], to initiate DNA repair, within 13 seconds. [146] => [147] => γH2AX, the phosphorylated form of [[H2AFX|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.{{cite journal |vauthors=Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM |title=DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139 |journal=J. Biol. Chem. |volume=273 |issue=10 |pages=5858–68 |year=1998 |pmid=9488723 |doi= 10.1074/jbc.273.10.5858|doi-access=free }} 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. The extent of chromatin with phosphorylated γH2AX is about two million base pairs at the site of a DNA double-strand break. γH2AX does not, itself, cause chromatin decondensation, but within 30 seconds of irradiation, [[RNF8]] protein can be detected in association with γH2AX.{{cite journal |vauthors=Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, Lukas J |title=RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins |journal=Cell |volume=131 |issue=5 |pages=887–900 |year=2007 |pmid=18001824 |doi=10.1016/j.cell.2007.09.040 |s2cid=14232192 |doi-access=free }} RNF8 mediates extensive chromatin decondensation, through its subsequent interaction with [[CHD4]],{{cite journal |vauthors=Luijsterburg MS, Acs K, Ackermann L, Wiegant WW, Bekker-Jensen S, Larsen DH, Khanna KK, van Attikum H, Mailand N, Dantuma NP |title=A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure |journal=EMBO J. |volume=31 |issue=11 |pages=2511–27 |year=2012 |pmid=22531782 |pmc=3365417 |doi=10.1038/emboj.2012.104 }} a component of the nucleosome remodeling and deacetylase complex [[Mi-2/NuRD complex|NuRD]]. [148] => [149] => 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. [150] => [151] => ==Methods to investigate chromatin== [152] => [[File:Heterochromatic versus euchromatic nuclei.jpg|thumb|Microscopy of heterochromatic versus euchromatic nuclei (H&E stain).]] [153] => [[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{{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 }} or [[pheochromocytoma]].{{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 }}]] [154] => [[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}}]] [155] => # '''[[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.{{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 }} 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.{{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 }} [156] => # '''[[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. [157] => # '''[[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.{{Cite journal [158] => | last1 = Giresi [159] => | first1 = Paul G. [160] => | last2 = Kim [161] => | first2 = Jonghwan [162] => | last3 = McDaniell [163] => | first3 = Ryan M. [164] => | last4 = Iyer [165] => | first4 = Vishwanath R. [166] => | last5 = Lieb [167] => | first5 = Jason D. [168] => | date = 2007-06-01 [169] => | title = FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin [170] => | journal = Genome Research [171] => | volume = 17 [172] => | issue = 6 [173] => | pages = 877–885 [174] => | doi = 10.1101/gr.5533506 [175] => | issn = 1088-9051 [176] => | pmc = 1891346 [177] => | pmid = 17179217 [178] => }} [179] => # '''[[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. [180] => # '''[[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.{{Cite journal [181] => | last1 = Galas [182] => | first1 = D. J. [183] => | last2 = Schmitz [184] => | first2 = A. [185] => | date = 1978-09-01 [186] => | title = DNAse footprinting: a simple method for the detection of protein-DNA binding specificity [187] => | journal = Nucleic Acids Research [188] => | volume = 5 [189] => | issue = 9 [190] => | pages = 3157–3170 [191] => | issn = 0305-1048 [192] => | pmc = 342238 [193] => | pmid = 212715 [194] => | doi=10.1093/nar/5.9.3157 [195] => }} [196] => # '''MNase-seq''' (Micrococcal Nuclease sequencing) uses the [[micrococcal nuclease]] enzyme to identify nucleosome positioning throughout the genome.{{Cite book [197] => | last1 = Cui [198] => | first1 = Kairong [199] => | last2 = Zhao [200] => | first2 = Keji [201] => | title = Chromatin Remodeling [202] => | chapter = Genome-Wide Approaches to Determining Nucleosome Occupancy in Metazoans Using MNase-Seq [203] => | date = 2012-01-01 [204] => | volume = 833 [205] => | pages = 413–419 [206] => | doi = 10.1007/978-1-61779-477-3_24 [207] => | issn = 1940-6029 [208] => | pmc = 3541821 [209] => | pmid = 22183607 [210] => | series = Methods in Molecular Biology [211] => | isbn = 978-1-61779-476-6 [212] => }}{{Cite journal [213] => | last1 = Buenrostro [214] => | first1 = Jason D. [215] => | last2 = Giresi [216] => | first2 = Paul G. [217] => | last3 = Zaba [218] => | first3 = Lisa C. [219] => | last4 = Chang [220] => | first4 = Howard Y. [221] => | last5 = Greenleaf [222] => | first5 = William J. [223] => | date = 2013-12-01 [224] => | title = Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position [225] => | journal = Nature Methods [226] => | volume = 10 [227] => | issue = 12 [228] => | pages = 1213–1218 [229] => | doi = 10.1038/nmeth.2688 [230] => | issn = 1548-7105 [231] => | pmc = 3959825 [232] => | pmid = 24097267 [233] => }} [234] => # '''[[Chromosome conformation capture]]''' determines the spatial organization of chromatin in the nucleus, by inferring genomic locations that physically interact. [235] => # '''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.{{Cite journal [236] => | vauthors = Mieczkowski J, Cook A, Bowman SK, Mueller B, Alver BH, Kundu S, Deaton AM, Urban JA, Larschan E, Park PJ, Kingston RE, Tolstorukov MY [237] => | date = 2016-05-06 [238] => | title = MNase titration reveals differences between nucleosome occupancy and chromatin accessibility. [239] => | journal = Nature Communications [240] => | volume = 7 [241] => | pages = 11485 [242] => | doi = 10.1038/ncomms11485 [243] => | pmc = 4859066 [244] => | pmid = 27151365 [245] => | bibcode = 2016NatCo...711485M [246] => }} [247] => [248] => ==Chromatin and knots== [249] => [250] => 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.{{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 }} [251] => [252] => ==Chromatin: alternative definitions== [253] => [254] => The term, introduced by [[Walther Flemming]], has multiple meanings: [255] => # '''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. [256] => # '''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. [257] => # '''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. [258] => [259] => 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.{{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 }} [260] => [261] => Chromatin Remodeling: [262] => [263] => Chromatin remodeling can result from covalent modification of histones that physically remodel, move or remove nucleosomes.{{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}} Studies of Sanosaka et al 2022, says that Chromatin remodeler CHD7 regulate cell type-specific gene expression in human neural crest cells. {{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}} [264] => [265] => ==Nobel Prizes== [266] => [267] => The following scientists were recognized for their contributions to chromatin research with [[Nobel Prize]]s: [268] => {| class="wikitable" [269] => |- [270] => !Year [271] => !Who [272] => !Award [273] => |- [274] => |1910 [275] => |[[Albrecht Kossel]] (University of Heidelberg) [276] => | [[Nobel Prize in Physiology or Medicine]] for his discovery of the five nuclear bases: [[adenine]], [[cytosine]], [[guanine]], [[thymine]], and [[uracil]]. [277] => |- [278] => |1933 [279] => |[[Thomas Hunt Morgan]] (California Institute of Technology) [280] => |[[Nobel Prize in Physiology or Medicine]] for his discoveries of the role played by the gene and chromosome in heredity, based on his studies of the white-eyed mutation in the fruit fly ''Drosophila''.[https://www.nobelprize.org/nobel_prizes/medicine/laureates/1933/morgan-article.html "Thomas Hunt Morgan and His Legacy".] Nobelprize.org. 7 Sep 2012 [281] => |- [282] => |1962 [283] => |[[Francis Crick]], [[James D. Watson|James Watson]] and [[Maurice Wilkins]] (MRC Laboratory of Molecular Biology, Harvard University and London University respectively) [284] => |[[Nobel Prize in Physiology or Medicine]] for their discoveries of the double helix structure of DNA and its significance for information transfer in living material. [285] => |- [286] => |1982 [287] => |[[Aaron Klug]] (MRC Laboratory of Molecular Biology) [288] => |[[Nobel Prize in Chemistry]] "for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes" [289] => |- [290] => |1993 [291] => |[[Richard J. Roberts]] and [[Phillip A. Sharp]] [292] => |[[Nobel Prize in Physiology]] "for their independent discoveries of [[split genes]]," in which DNA sections called [[exons]] express proteins, and are interrupted by DNA sections called [[introns]], which do not express proteins. [293] => |- [294] => |2006 [295] => |[[Roger Kornberg]] (Stanford University) [296] => |[[Nobel Prize in Chemistry]] for his discovery of the mechanism by which DNA is transcribed into messenger RNA. [297] => |} [298] => [299] => ==See also== [300] => [301] => {{div col|colwidth=30em}} [302] => * [[Active chromatin sequence]] [303] => * [[Chromatid]] [304] => * [[DAnCER (database)|DAnCER]] database (2010) [305] => * [[Epigenetics]] [306] => * [[Histone-modifying enzymes]] [307] => * [[Position-effect variegation]] [308] => * [[Transcriptional bursting]] [309] => {{div col end}} [310] => [311] => ==Notes== [312] => [313] => {{notelist}} [314] => [315] => ==References== [316] => [317] => {{reflist}} [318] => [319] => ===Additional sources=== [320] => [321] => * Cooper, Geoffrey M. 2000. The Cell, 2nd edition, A Molecular Approach. Chapter 4.2 [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=cooper&part=A618#A620 Chromosomes and Chromatin.] [322] => * {{cite journal | last1 = Corces | first1 = V. G. | year = 1995 | title = Chromatin insulators. Keeping enhancers under control | journal = Nature | volume = 376 | issue = 6540| pages = 462–463 | doi=10.1038/376462a0 | pmid=7637775| bibcode = 1995Natur.376..462C| s2cid = 26494996 | doi-access = free }} [323] => * Cremer, T. 1985. Von der Zellenlehre zur Chromosomentheorie: Naturwissenschaftliche Erkenntnis und Theorienwechsel in der frühen Zell- und Vererbungsforschung, Veröffentlichungen aus der Forschungsstelle für Theoretische Pathologie der Heidelberger Akademie der Wissenschaften. Springer-Vlg., Berlin, Heidelberg. [324] => * Elgin, S. C. R. (ed.). 1995. Chromatin Structure and Gene Expression, vol. 9. IRL Press, Oxford, New York, Tokyo. [325] => * {{cite journal | last1 = Gerasimova | first1 = T. I. | last2 = Corces | first2 = V. G. | year = 1996 | title = Boundary and insulator elements in chromosomes | journal = Curr. Opin. Genet. Dev. | volume = 6 | issue = 2| pages = 185–192 | doi=10.1016/s0959-437x(96)80049-9| pmid = 8722175 | doi-access = free }} [326] => * {{cite journal | last1 = Gerasimova | first1 = T. I. | last2 = Corces | first2 = V. G. | year = 1998 | title = Polycomb and Trithorax group proteins mediate the function of a chromatin insulator | journal = Cell | volume = 92 | issue = 4| pages = 511–521 | doi=10.1016/s0092-8674(00)80944-7| pmid = 9491892 | s2cid = 8192263 | doi-access = free }} [327] => * {{cite journal | last1 = Gerasimova | first1 = T. I. | last2 = Corces | first2 = V. G. | s2cid = 22738830 | year = 2001 | title = CHROMATIN INSULATORS AND BOUNDARIES: Effects on Transcription and Nuclear Organization | journal = Annu Rev Genet | volume = 35 | pages = 193–208 | pmid = 11700282 | doi = 10.1146/annurev.genet.35.102401.090349 }} [328] => * {{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 }} [329] => * {{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 }} [330] => * Pollard, T., and W. Earnshaw. 2002. Cell Biology. Saunders. [331] => * Saumweber, H. 1987. Arrangement of Chromosomes in Interphase Cell Nuclei, p. 223-234. In W. Hennig (ed.), Structure and Function of Eucaryotic Chromosomes, vol. 14. Springer-Verlag, Berlin, Heidelberg. [332] => * {{cite journal | last1 = Sinden | first1 = R. R. | year = 2005 | title = Molecular biology: DNA twists and flips | journal = Nature | volume = 437 | issue = 7062| pages = 1097–8 | doi=10.1038/4371097a | pmid=16237426| bibcode = 2005Natur.437.1097S | s2cid = 4409092 | doi-access = free }} [333] => * Van Holde KE. 1989. Chromatin. New York: [[Springer Science+Business Media|Springer-Verlag]]. {{ISBN|0-387-96694-3}}. [334] => * Van Holde, K., J. Zlatanova, G. Arents, and E. Moudrianakis. 1995. Elements of chromatin structure: histones, nucleosomes, and fibres, p. 1-26. In S. C. R. Elgin (ed.), Chromatin structure and gene expression. IRL Press at Oxford University Press, Oxford. [335] => [336] => ==External links== [337] => * [https://www.youtube.com/watch?v=eYrQ0EhVCYA Chromatin, Histones & Cathepsin]; PMAP [[The Proteolysis Map]]-animation [338] => * [https://www.nature.com/subjects/chromatin ''Nature'' journal: recent chromatin publications and news] [339] => * [http://www.activemotif.com/documents/134.pdf Protocol for ''in vitro'' Chromatin Assembly] [340] => * [http://www.nature.com/encode/#/threads/chromatin-patterns-at-transcription-factor-binding-sites ENCODE threads Explorer] Chromatin patterns at transcription factor binding sites. [[Nature (journal)]] [341] => [342] => {{Chromo}} [343] => {{Nucleus}} [344] => {{Authority control}} [345] => {{portal bar|Biology|Science}} [346] => [347] => [[Category:Molecular genetics]] [348] => [[Category:Nuclear substructures]] [] => )
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Chromatin

Chromatin is the material that makes up the chromosomes in eukaryotic cells. It consists of DNA, RNA, and proteins, and is responsible for the packaging and organization of genetic information.

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It consists of DNA, RNA, and proteins, and is responsible for the packaging and organization of genetic information. Chromatin undergoes structural changes in different stages of the cell cycle, which allows for the regulation of gene expression and DNA replication. This page provides a comprehensive overview of chromatin, including its structure, composition, and functions. It also discusses the various types of chromatin modifications and their role in gene regulation. Additionally, the page delves into the relationship between chromatin and diseases, as well as the techniques used to study chromatin and its modifications.

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Adenine

Adenine is a nucleobase, which is a component of nucleotides, the basic building blocks of DNA and RNA.

Bird

Birds are a group of warm-blooded vertebrates characterized by feathers, beaks, wings, and the ability to lay eggs.

BRCA1

BRCA1, an abbreviation for Breast Cancer gene 1, is a human gene that produces a protein called breast cancer type 1 susceptibility protein.

Chromosome

A chromosome is a structure found in the cells of organisms that carries their genetic information.

Cytosine

Cytosine (symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA).

DNA

DNA, also known as deoxyribonucleic acid, is a molecule that carries the genetic instructions used in the growth, development, functioning, and reproduction of all known living organisms and many viruses.

Eukaryote

Eukaryotes are complex organisms whose cells contain a nucleus and other membrane-bound organelles.

Gene

Gene is a widely recognized online encyclopedia that provides information on a wide range of topics, including biology, genetics, and other related fields.

Guanine

Guanine (symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine (uracil in RNA).

Mitosis

Mitosis is a process of cell division that occurs in eukaryotic cells, leading to the production of two identical daughter cells.

Protein

Proteins are macromolecules found in all living organisms.