Editing Histone (section)

== Classes and variants ==
[[File:1aoi.jpg|thumb|270px|Histone heterooctamer (H3,H4,H2A,H2B) + DNA fragment, Frog]]
Five major families of histone proteins exist: [[Histone H1|H1/H5]], [[Histone H2A|H2A]], [[Histone H2B|H2B]], [[Histone H3|H3]], and [[Histone H4|H4]].<ref name="Nelson&Cox" /><ref name="HistoneDB">{{cite web | url = https://www.ncbi.nlm.nih.gov/projects/HistoneDB2.0 | title = Histone Variants Database 2.0  | access-date = 13 January 2017 | publisher= [[National Center for Biotechnology Information]]}}</ref><ref name="Bhasin_2006">{{cite journal | vauthors = Bhasin M, Reinherz EL, Reche PA | title = Recognition and classification of histones using support vector machine | journal = Journal of Computational Biology | volume = 13 | issue = 1 | pages = 102–12 | year = 2006 | pmid = 16472024 | doi = 10.1089/cmb.2006.13.102 | url = http://eprints.ucm.es/9328/1/31.Reche_etal_MI_2006.pdf | access-date = 2019-03-23 | archive-date = 2020-11-28 | archive-url = https://web.archive.org/web/20201128030045/http://eprints.ucm.es/9328/1/31.Reche_etal_MI_2006.pdf | url-status = dead }}</ref><ref name="HartlFreilfelder&Snyder">{{Cite book | vauthors = Hartl DL, Freifelder D, Snyder LA |year= 1988 |title= Basic Genetics |location= Boston |publisher= Jones and Bartlett Publishers |isbn= 978-0-86720-090-4 |url-access= registration |url= https://archive.org/details/basicgenetics0000hart }}</ref> Histones H2A, H2B, H3 and H4 are known as the core or nucleosomal histones, while histones H1/H5 are known as the linker histones.

The core histones all exist as [[Protein dimer|dimer]]s, which are similar in that they all possess the histone fold domain: three alpha helices linked by two loops. It is this helical structure that allows for interaction between distinct dimers, particularly in a head-tail fashion (also called the handshake motif).<ref>{{cite journal | vauthors = Mariño-Ramírez L, Kann MG, Shoemaker BA, Landsman D | title = Histone structure and nucleosome stability | journal = Expert Review of Proteomics | volume = 2 | issue = 5 | pages = 719–29 | date = October 2005 | pmid = 16209651 | pmc = 1831843 | doi = 10.1586/14789450.2.5.719 }}</ref> The resulting four distinct dimers then come together to form one octameric [[nucleosome]] core, approximately 63 Angstroms in diameter (a [[solenoid (DNA)]]-like particle). Around 146 [[base pairs]] (bp) of DNA wrap around this core particle 1.65 times in a left-handed super-helical turn to give a particle of around 100 Angstroms across.<ref name="pmid9305837">{{cite journal |vauthors=Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ |date=September 1997 |title=Crystal structure of the nucleosome core particle at 2.8 A resolution |url=https://www.nature.com/articles/38444 |journal=Nature |volume=389 |issue=6648 |pages=251–60 |bibcode=1997Natur.389..251L |doi=10.1038/38444 |pmid=9305837 |s2cid=4328827|url-access=subscription }} {{PDB|1AOI}}</ref>  The linker histone H1 binds the nucleosome at the entry and exit sites of the DNA, thus locking the DNA into place<ref>{{cite book | vauthors = Farkas D |title=DNA simplified: the hitchhiker's guide to DNA |publisher=AACC Press |location=Washington, D.C. |year=1996 |isbn=978-0-915274-84-0 }}</ref> and allowing the formation of higher order structure.  The most basic such formation is the 10&nbsp;nm fiber or beads on a string conformation.  This involves the wrapping of DNA around nucleosomes with approximately 50 base pairs of [[DNA]] separating each pair of [[nucleosome]]s (also referred to as linker [[DNA]]). Higher-order structures include the 30&nbsp;nm fiber (forming an irregular zigzag) and 100&nbsp;nm fiber, these being the structures found in normal cells. During mitosis and meiosis, the condensed [[chromosome]]s are assembled through interactions between nucleosomes and other regulatory proteins.

Histones are subdivided into canonical replication-dependent histones, whose genes are expressed during the [[S-phase]] of the [[cell cycle]] and replication-independent [[histone variants]], expressed during the whole cell cycle. In mammals, genes encoding canonical histones are typically clustered along chromosomes in 4 different highly-[[Conserved sequence|conserved]] loci, lack [[intron]]s and use a stem loop structure at the [[3' end]] instead of a [[polyA tail]]. Genes encoding histone variants are usually not clustered, have introns and their mRNAs are regulated with polyA tails.<ref name="Seal-2022">{{cite journal | vauthors = Seal RL, Denny P, Bruford EA, Gribkova AK, Landsman D, Marzluff WF, McAndrews M, Panchenko AR, Shaytan AK, Talbert PB | title = A standardized nomenclature for mammalian histone genes | journal = Epigenetics & Chromatin | volume = 15 | issue = 1 | pages = 34 | date = October 2022 | pmid = 36180920 | pmc = 9526256 | doi = 10.1186/s13072-022-00467-2 | doi-access = free }}</ref> Complex multicellular organisms typically have a higher number of histone variants providing a variety of different functions. Functionally, histone variants contribute to transcriptional control, epigenetic memory, and DNA repair, serving specialized functions beyond nucleosome packaging which plays distinct roles in chromatin dynamics. For example, [[H2A.Z]] is enriched at regulatory elements and promoters of actively transcribed genes, where it modulates nucleosome stability and transcription factor binding. In contrast, H3.3, a replacement variant of [[Histone H3]], is associated with active transcription and is preferentially deposited at enhancer elements and transcribed gene bodies. Another critical variant, [[CENPA]], replaces H3 in centromeric nucleosomes, providing a structural foundation essential for chromosome segregation.<ref name="Venkatesh_2015" />

Variants also play essential roles in [[DNA repair]]. Variants such as H2A.X are phosphorylated at sites of DNA damage, marking regions for recruitment of repair proteins. This modification, commonly referred to as γH2A.X, serves as a key signal in the cellular response to [[double-strand breaks]], facilitating efficient DNA repair processes. Defects in histone variant regulation have been linked to [[genome instability]], a hallmark of many cancers and age-related diseases.<ref>{{cite journal | vauthors = Vardabasso C, Hasson D, Ratnakumar K, Chung CY, Duarte LF, Bernstein E | title = Histone variants: emerging players in cancer biology | journal = Cellular and Molecular Life Sciences | volume = 71 | issue = 3 | pages = 379–404 | date = February 2014 | pmid = 23652611 | pmc = 4025945 | doi = 10.1007/s00018-013-1343-z }}</ref> 

Recent data are accumulating about the roles of diverse histone variants highlighting the functional links between variants and the delicate regulation of organism development.<ref>{{cite journal | vauthors = Jang CW, Shibata Y, Starmer J, Yee D, Magnuson T | title = Histone H3.3 maintains genome integrity during mammalian development | journal = Genes & Development | volume = 29 | issue = 13 | pages = 1377–1392 | date = July 2015 | pmid = 26159997 | pmc = 4511213 | doi = 10.1101/gad.264150.115 | doi-access = free }}</ref> Histone variants proteins from different organisms, their classification and variant specific features can be found in [https://www.ncbi.nlm.nih.gov/projects/HistoneDB2.0/ "HistoneDB 2.0 - Variants"] database.<ref>{{cite journal | vauthors = Draizen EJ, Shaytan AK, Mariño-Ramírez L, Talbert PB, Landsman D, Panchenko AR | title = HistoneDB 2.0: a histone database with variants--an integrated resource to explore histones and their variants | journal = Database | volume = 2016 | pages = baw014 | date = 2016 | pmid = 26989147 | pmc = 4795928 | doi = 10.1093/database/baw014 }}</ref><ref>{{cite journal | vauthors = El Kennani S, Adrait A, Shaytan AK, Khochbin S, Bruley C, Panchenko AR, Landsman D, Pflieger D, Govin J | title = MS_HistoneDB, a manually curated resource for proteomic analysis of human and mouse histones | journal = Epigenetics & Chromatin | volume = 10 | pages = 2 | date = 2017 | pmid = 28096900 | pmc = 5223428 | doi = 10.1186/s13072-016-0109-x | doi-access = free }}</ref> Several [[Pseudogene|pseudogenes]] have also been discovered and identified in very close sequences of their respective functional ortholog genes.<ref>{{cite journal | vauthors = Marashi F, Prokopp K, Stein J, Stein G | title = Evidence for a human histone gene cluster containing H2B and H2A pseudogenes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 7 | pages = 1936–1940 | date = April 1984 | pmid = 6326092 | pmc = 345411 | doi = 10.1073/pnas.81.7.1936 | doi-access = free | bibcode = 1984PNAS...81.1936M }}</ref><ref>{{cite journal | vauthors = Kardalinou E, Eick S, Albig W, Doenecke D | title = Association of a human H1 histone gene with an H2A pseudogene and genes encoding H2B.1 and H3.1 histones | journal = Journal of Cellular Biochemistry | volume = 52 | issue = 4 | pages = 375–383 | date = August 1993 | pmid = 8227173 | doi = 10.1002/jcb.240520402 | s2cid = 42454232 }}</ref>

The following is a list of human histone proteins, genes and pseudogenes:<ref name="Seal-2022" />
{| class="wikitable"
!Super family
!Family
!Replication-dependent genes
!Replication-independent genes
!Pseudogenes
|-
| align="center" |Linker
| align="center" |[[Histone H1|H1]]
|[[H1-1]], [[H1-2]], [[H1-3]], [[H1-4]], [[H1-5]], [[H1-6]]
|[[H1-0]], [[H1-7]], [[H1-8]], [[H1-10]]
|[[HILS1|H1-9P]], [[HIST1H1PS1|H1-12P]]
|-
| rowspan="4" align="center" |Core
| align="center" |[[Histone H2A|H2A]]
|[[H2AC1]], [[H2AC4]], [[H2AC6]], [[H2AC7]], [[H2AC8]], [[H2AC11]], [[H2AC12]], [[H2AC13]], [[H2AC14]], [[H2AC15]], [[H2AC16]], [[H2AC17]], [[H2AC18]], [[HIST2H2AA4|H2AC19]], [[H2AC20]], [[H2AC21]], [[H2AC25]]
|[[H2AZ1]], [[H2AZ2]], [[MACROH2A1]], [[MACROH2A2]], [[H2AX]], [[H2AJ]], [[H2AB1]], [[H2AB2]], [[H2AB3]], [[HYPM|H2AP]], H2AL1Q, H2AL3
|[[HIST1H2APS1|H2AC2P]], [[HIST1H2APS2|H2AC3P]], [[HIST1H2APS5|H2AC5P]], [[HIST1H2APS3|H2AC9P]], [[HIST1H2APS4|H2AC10P]], H2AQ1P, H2AL1MP
|-
| align="center" |[[Histone H2B|H2B]]
|[[H2BC1]], [[H2BC3]], [[H2BC4]], [[H2BC5]], [[H2BC6]], [[H2BC7]], [[H2BC8]], [[H2BC9]], [[H2BC10]], [[H2BC11]], [[H2BC12]], [[H2BC13]], [[H2BC14]], [[H2BC15]], [[H2BC17]], [[H2BC18]], [[H2BC21]], [[H2BC26]], [[H2BC12L]]
|[[H2BE1|H2BK1]], [[H2BW1]], [[H2BW2]], H2BW3P, H2BN1
|[[HIST1H2BPS1|H2BC2P]], [[HIST1H2BPS2|H2BC16P]], [[HIST2H2BD|H2BC19P]], [[HIST2H2BC|H2BC20P]], [[HIST3H2BA|H2BC27P]], [[H2ABP4|H2BL1P]], H2BW3P, [[H2BFXP|H2BW4P]]
|-
| align="center" |[[Histone H3|H3]]
|[[H3C1]], [[H3C2]], [[H3C3]], [[H3C4]], [[H3C6]], [[H3C7]], [[H3C8]], [[H3C10]], [[H3C11]], [[H3C12]], [[HIST2H3D|H3C13]], [[H3C14]], [[H3C15]], [[H3-4]]
|[[H3-3A]], [[H3-3B]], [[H3F3C|H3-5]], [[H3-7]], H3Y1, H3Y2'','' [[CENPA]]
|H3C5P, [[HIST1H3PS1|H3C9P]], [[H3F3AP6|H3P16]], [[H3F3AP5|H3P44]]
|-
| align="center" |[[Histone H4|H4]]
|[[H4C1]], [[H4C2]], [[H4C3]], [[H4C4]], [[H4C5]], [[H4C6]], [[H4C7]], [[H4C8]], [[H4C9]], [[H4C11]], [[H4C12]], [[H4C13]], [[H4C14]], [[HIST2H4B|H4C15]]
|[[H4C16]]
|[[HIST1H4PS1|H4C10P]]
|}