Editing Histone (section)

==== Repressed genes ====

Three histone modifications are particularly associated with repressed genes:
;''Trimethylation of H3 lysine 27 (H3K27me3)'': This histone modification is deposited by the [[polycomb]] complex PRC2.<ref>{{cite journal | vauthors = Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D | title = Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein | journal = Genes & Development | volume = 16 | issue = 22 | pages = 2893–905 | date = November 2002 | pmid = 12435631 | pmc = 187479 | doi = 10.1101/gad.1035902 }}</ref> It is a clear marker of gene repression,<ref name="pmid12351676">{{cite journal |vauthors=Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y |date=November 2002 |title=Role of histone H3 lysine 27 methylation in Polycomb-group silencing |url=https://www.science.org/doi/10.1126/science.1076997 |journal=Science |volume=298 |issue=5595 |pages=1039–43 |bibcode=2002Sci...298.1039C |doi=10.1126/science.1076997 |pmid=12351676 |s2cid=6265267}}</ref> and is likely bound by other proteins to exert a repressive function. Another [[polycomb]] complex, PRC1, can bind [[H3K27me3]]<ref name="pmid12351676"/> and adds the histone modification H2AK119Ub which aids chromatin compaction.<ref>{{cite journal | vauthors = de Napoles M, Mermoud JE, Wakao R, Tang YA, Endoh M, Appanah R, Nesterova TB, Silva J, Otte AP, Vidal M, Koseki H, Brockdorff N | title = Polycomb group proteins Ring1A/B link ubiquitylation of histone H2A to heritable gene silencing and X inactivation | journal = Developmental Cell | volume = 7 | issue = 5 | pages = 663–76 | date = November 2004 | pmid = 15525528 | doi = 10.1016/j.devcel.2004.10.005 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P, Jones RS, Zhang Y | title = Role of histone H2A ubiquitination in Polycomb silencing | journal = Nature | volume = 431 | issue = 7010 | pages = 873–8 | date = October 2004 | pmid = 15386022 | doi = 10.1038/nature02985 | s2cid = 4344378 | bibcode = 2004Natur.431..873W | hdl = 10261/73732 }}</ref> Based on this data it appears that PRC1 is recruited through the action of PRC2, however, recent studies show that PRC1 is recruited to the same sites in the absence of PRC2.<ref>{{cite journal | vauthors = Tavares L, Dimitrova E, Oxley D, Webster J, Poot R, Demmers J, Bezstarosti K, Taylor S, Ura H, Koide H, Wutz A, Vidal M, Elderkin S, Brockdorff N | title = RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3 | journal = Cell | volume = 148 | issue = 4 | pages = 664–78 | date = February 2012 | pmid = 22325148 | pmc = 3281992 | doi = 10.1016/j.cell.2011.12.029 }}</ref><ref>{{cite journal | vauthors = Gao Z, Zhang J, Bonasio R, Strino F, Sawai A, Parisi F, Kluger Y, Reinberg D | title = PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes | journal = Molecular Cell | volume = 45 | issue = 3 | pages = 344–56 | date = February 2012 | pmid = 22325352 | pmc = 3293217 | doi = 10.1016/j.molcel.2012.01.002 }}</ref>
;''Di and tri-methylation of H3 lysine 9 (H3K9me2/3)'': H3K9me2/3 is a well-characterised marker for [[heterochromatin]], and is therefore strongly associated with gene repression. The formation of heterochromatin has been best studied in the yeast ''[[Schizosaccharomyces pombe]]'', where it is initiated by recruitment of the [[RNA-induced transcriptional silencing]] (RITS) complex to double stranded RNAs produced from [[centromeric]] repeats.<ref>{{cite journal | vauthors = Verdel A, Jia S, Gerber S, Sugiyama T, Gygi S, Grewal SI, Moazed D | title = RNAi-mediated targeting of heterochromatin by the RITS complex | journal = Science | volume = 303 | issue = 5658 | pages = 672–6 | date = January 2004 | pmid = 14704433 | pmc = 3244756 | doi = 10.1126/science.1093686 | bibcode = 2004Sci...303..672V }}</ref> RITS recruits the Clr4 [[histone methyltransferase]] which deposits H3K9me2/3.<ref>{{cite journal |vauthors=Rea S, Eisenhaber F, O'Carroll D, Strahl BD, Sun ZW, Schmid M, Opravil S, Mechtler K, Ponting CP, Allis CD, Jenuwein T |date=August 2000 |title=Regulation of chromatin structure by site-specific histone H3 methyltransferases |url=https://www.nature.com/articles/35020506 |journal=Nature |volume=406 |issue=6796 |pages=593–9 |bibcode=2000Natur.406..593R |doi=10.1038/35020506 |pmid=10949293 |s2cid=205008015}}</ref> This process is called [[histone methylation]]. H3K9Me2/3 serves as a binding site for the recruitment of Swi6 ([[heterochromatin protein 1]] or HP1, another classic heterochromatin marker)<ref>{{cite journal |vauthors=Bannister AJ, Zegerman P, Partridge JF, Miska EA, Thomas JO, Allshire RC, Kouzarides T |date=March 2001 |title=Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain |url=https://www.nature.com/articles/35065138 |journal=Nature |volume=410 |issue=6824 |pages=120–4 |bibcode=2001Natur.410..120B |doi=10.1038/35065138 |pmid=11242054 |s2cid=4334447}}</ref><ref>{{cite journal |vauthors=Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T |date=March 2001 |title=Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins |url=https://www.nature.com/articles/35065132 |journal=Nature |volume=410 |issue=6824 |pages=116–20 |bibcode=2001Natur.410..116L |doi=10.1038/35065132 |pmid=11242053 |s2cid=4331863}}</ref> which in turn recruits further repressive activities including histone modifiers such as [[histone deacetylase]]s and [[histone methyltransferase]]s.<ref>{{cite journal | vauthors = Bajpai G, Jain I, Inamdar MM, Das D, Padinhateeri R | title = Binding of DNA-bending non-histone proteins destabilizes regular 30-nm chromatin structure | journal = PLOS Computational Biology | volume = 13 | issue = 1 | pages = e1005365 | date = January 2017 | pmid = 28135276 | pmc = 5305278 | doi = 10.1371/journal.pcbi.1005365 | bibcode = 2017PLSCB..13E5365B | doi-access = free }}</ref>
;''Trimethylation of H4 lysine 20 ([[H4K20me]]3)'': This modification is tightly associated with heterochromatin,<ref name="pmid15145825">{{cite journal | vauthors = Schotta G, Lachner M, Sarma K, Ebert A, Sengupta R, Reuter G, Reinberg D, Jenuwein T | title = A silencing pathway to induce H3-K9 and H4-K20 trimethylation at constitutive heterochromatin | journal = Genes & Development | volume = 18 | issue = 11 | pages = 1251–62 | date = June 2004 | pmid = 15145825 | pmc = 420351 | doi = 10.1101/gad.300704 }}</ref><ref>{{cite journal | vauthors = Kourmouli N, Jeppesen P, Mahadevhaiah S, Burgoyne P, Wu R, Gilbert DM, Bongiorni S, Prantera G, Fanti L, Pimpinelli S, Shi W, Fundele R, Singh PB | title = Heterochromatin and tri-methylated lysine 20 of histone H4 in animals | journal = Journal of Cell Science | volume = 117 | issue = Pt 12 | pages = 2491–501 | date = May 2004 | pmid = 15128874 | doi = 10.1242/jcs.01238 | doi-access = free }}</ref> although its functional importance remains unclear. This mark is placed by the Suv4-20h methyltransferase, which is at least in part recruited by [[heterochromatin protein 1]].<ref name="pmid15145825"/>