Polycomb-group proteins

{{short description|Family of proteins that play a role in chromatin remodeling}} '''Polycomb-group proteins''' ('''PcG proteins''') are a family of protein complexes first discovered in fruit flies that can remodel chromatin such that epigenetic silencing of genes takes place. Polycomb-group proteins are well known for silencing Hox genes through modulation of chromatin structure during embryonic development in fruit flies (''Drosophila melanogaster''). They derive their name from the fact that the first sign of a decrease in PcG function is often a homeotic transformation of posterior legs towards anterior legs, which have a characteristic comb-like set of bristles.<ref name= Portoso >{{cite book |chapter-url=https://books.google.com/books?id=r67Lrf9r9XEC&pg=PA29 |vauthors=Portoso M, Cavalli G | editor = Morris KV | 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 | pages = 29–44 }}</ref>

== In insects == In ''Drosophila'', the Trithorax-group (trxG) and Polycomb-group (PcG) proteins act antagonistically and interact with chromosomal elements, termed Cellular Memory Modules (CMMs). Trithorax-group (trxG) proteins maintain the active state of gene expression while the Polycomb-group (PcG) proteins counteract this activation with a repressive function that is stable over many cell generations and can only be overcome by germline differentiation processes. Polycomb Gene complexes or PcG silencing consist of at least three kinds of multiprotein complex Polycomb Repressive Complex 1 (PRC1), PRC2 and PhoRC. These complexes work together to carry out their repressive effect. PcGs proteins are evolutionarily conserved and exist in at least two separate protein complexes; the PcG repressive complex 1 (PRC1) and the PcG repressive complex 2–4 (PRC2/3/4). PRC2 catalyzes trimethylation of lysine 27 on histone H3 (H3K27me2/3), while PRC1 mono- ubiquitinates histone H2A on lysine 119 (H2AK119Ub1).

== In mammals == In mammals Polycomb Group gene expression is important in many aspects of development like homeotic gene regulation and X chromosome inactivation, being recruited to the inactive X by Xist RNA, the master regulator of XCI<ref>{{cite journal | vauthors = Ku M, Koche RP, Rheinbay E, Mendenhall EM, Endoh M, Mikkelsen TS, Presser A, Nusbaum C, Xie X, Chi AS, Adli M, Kasif S, Ptaszek LM, Cowan CA, Lander ES, Koseki H, Bernstein BE | title = Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains | journal = PLOS Genetics | volume = 4 | issue = 10 | article-number = e1000242 | date = October 2008 | pmid = 18974828 | pmc = 2567431 | doi = 10.1371/journal.pgen.1000242 | doi-access = free }}</ref> or embryonic stem cell self-renewal.<ref>Heurtier, V., Owens, N., Gonzalez, I. et al. The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells. Nat Commun 10, 1109 (2019). https://doi.org/10.1038/s41467-019-09041-z</ref> The Bmi1 polycomb ring finger protein promotes neural stem cell self-renewal.<ref name=pmid15964994>{{cite journal | vauthors = Molofsky AV, He S, Bydon M, Morrison SJ, Pardal R | title = Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways | journal = Genes & Development | volume = 19 | issue = 12 | pages = 1432–7 | date = June 2005 | pmid = 15964994 | pmc = 1151659 | doi = 10.1101/gad.1299505 }}</ref><ref name=pmid14722607>{{cite journal | vauthors = Park IK, Morrison SJ, Clarke MF | title = Bmi1, stem cells, and senescence regulation | journal = The Journal of Clinical Investigation | volume = 113 | issue = 2 | pages = 175–9 | date = January 2004 | pmid = 14722607 | pmc = 311443 | doi = 10.1172/JCI20800 }}</ref> Murine null mutants in PRC2 genes are embryonic lethals while most PRC1 mutants are live born homeotic mutants that die perinatally. In contrast overexpression of PcG proteins correlates with the severity and invasiveness of several cancer types.<ref name="pmid18447587">{{cite journal | vauthors = Sauvageau M, Sauvageau G | title = Polycomb group genes: keeping stem cell activity in balance | journal = PLOS Biology | volume = 6 | issue = 4 | article-number = e113 | date = April 2008 | pmid = 18447587 | pmc = 2689701 | doi = 10.1371/journal.pbio.0060113 | doi-access = free }}</ref> The mammalian PRC1 core complexes are very similar to Drosophila. Polycomb Bmi1 is known to regulate ink4 locus (p16^Ink4a, p19^Arf).<ref name="pmid15964994" /><ref name=pmid20716961>{{cite journal | vauthors = Popov N, Gil J | title = Epigenetic regulation of the INK4b-ARF-INK4a locus: in sickness and in health | journal = Epigenetics | volume = 5 | issue = 8 | pages = 685–90 | year = 2010 | pmid = 20716961 | pmc = 3052884 | doi = 10.4161/epi.5.8.12996 | url = http://www.landesbioscience.com/journals/epigenetics/article/12996/?nocache=2141572894 | format = PDF }}</ref>

Regulation of Polycomb-group proteins at bivalent chromatin sites is performed by SWI/SNF complexes, which oppose the accumulation of Polycomb complexes through ATP-dependent eviction.<ref>{{cite journal | vauthors = Stanton BZ, Hodges C, Calarco JP, Braun SM, Ku WL, Kadoch C, Zhao K, Crabtree GR | title = Smarca4 ATPase mutations disrupt direct eviction of PRC1 from chromatin | journal = Nature Genetics | volume = 49 | issue = 2 | pages = 282–288 | date = February 2017 | pmc = 5373480 | doi = 10.1038/ng.3735 | pmid = 27941795 }}</ref>

=== Recruitment in X chromosome inactivation ===

X chromosome inactivation (XCI) is the phenomenon that has been selected during the evolution to balance X-linked gene dosage between XX females and XY males.<ref>{{cite journal | vauthors = Nora EP, Heard E | title = X chromosome inactivation: when dosage counts | journal = Cell | volume = 139 | issue = 5 | pages = 865–7 | date = November 2009 | pmid = 19945374 | doi = 10.1016/j.cell.2009.11.009 | doi-access = free }}</ref> It is can be divided into two phases: the establishment phase when gene silencing is reversible, and maintenance phase when gene silencing becomes irreversible.<ref>{{cite journal | vauthors = Wutz A, Jaenisch R | title = A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation | journal = Molecular Cell | volume = 5 | issue = 4 | pages = 695–705 | date = April 2000 | pmid = 10882105 | doi = 10.1016/s1097-2765(00)80248-8 | doi-access = free }}</ref> During the establishment phase XCI, Xist RNA, the master regulator of this process, is monoallelically upregulated,<ref>{{cite journal | vauthors = Cerase A, Young AN, Ruiz NB, Buness A, Sant GM, Arnold M, Di Giacomo M, Ascolani M, Kumar M, Hierholzer A, Trigiante G, Marzi SJ, Avner P | display-authors = 6 | title = Chd8 regulates X chromosome inactivation in mouse through fine-tuning control of Xist expression | journal = Communications Biology | volume = 4 | issue = 1 | article-number = 485 | date = April 2021 | pmid = 33859315 | doi = 10.1038/s42003-021-01945-1 | pmc = 8050208 | doi-access = free }}</ref> and it spreads ''in cis'' along the future inactive X (Xi), relocating<!-- ? --> to the nuclear periphery.<ref>{{cite journal | vauthors = Chen CK, Blanco M, Jackson C, Aznauryan E, Ollikainen N, Surka C, Chow A, Cerase A, McDonel P, Guttman M | display-authors = 6 | title = Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing | journal = Science | volume = 354 | issue = 6311 | pages = 468–472 | date = October 2016 | pmid = 27492478 | doi = 10.1126/science.aae0047 | bibcode = 2016Sci...354..468C | doi-access = free }}</ref><ref>{{cite journal | vauthors = Young AN, Perlas E, Ruiz-Blanes N, Hierholzer A, Pomella N, Martin-Martin B, Liverziani A, Jachowicz JW, Giannakouros T, Cerase A | display-authors = 6 | title = Deletion of LBR N-terminal domains recapitulates Pelger-Huet anomaly phenotypes in mouse without disrupting X chromosome inactivation | journal = Communications Biology | volume = 4 | issue = 1 | article-number = 478 | date = April 2021 | pmid = 33846535 | doi = 10.1038/s42003-021-01944-2 | pmc = 8041748 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Zhang LF, Huynh KD, Lee JT | title = Perinucleolar targeting of the inactive X during S phase: evidence for a role in the maintenance of silencing | journal = Cell | volume = 129 | issue = 4 | pages = 693–706 | date = May 2007 | pmid = 17512404 | doi = 10.1016/j.cell.2007.03.036 | doi-access = free }}</ref> and recruits repressive chromatin-remodelling complexes,<ref>{{cite journal | vauthors = Chow J, Heard E | title = X inactivation and the complexities of silencing a sex chromosome | journal = Current Opinion in Cell Biology | volume = 21 | issue = 3 | pages = 359–66 | date = June 2009 | pmid = 19477626 | doi = 10.1016/j.ceb.2009.04.012 }}</ref> including proteins of the polycomb repressive complexes.<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 | display-authors = 6 | 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 = Plath K, Fang J, Mlynarczyk-Evans SK, Cao R, Worringer KA, Wang H, de la Cruz CC, Otte AP, Panning B, Zhang Y | display-authors = 6 | title = Role of histone H3 lysine 27 methylation in X inactivation | journal = Science | volume = 300 | issue = 5616 | pages = 131–5 | date = April 2003 | pmid = 12649488 | doi = 10.1126/science.1084274 | bibcode = 2003Sci...300..131P | s2cid = 28578313 | doi-access = free }}</ref> Whether Xist directly recruits polycomb repressive complex 2 (PRC2) to the chromatin<ref>{{cite journal | vauthors = Zhao J, Sun BK, Erwin JA, Song JJ, Lee JT | title = Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome | journal = Science | volume = 322 | issue = 5902 | pages = 750–6 | date = October 2008 | pmid = 18974356 | pmc = 2748911 | doi = 10.1126/science.1163045 | bibcode = 2008Sci...322..750Z }}</ref> or this recruitment is the consequence of Xist-mediated changes on the chromatin has been the object of intense debate.<ref>{{cite journal | vauthors = Cerase A, Smeets D, Tang YA, Gdula M, Kraus F, Spivakov M, Moindrot B, Leleu M, Tattermusch A, Demmerle J, Nesterova TB, Green C, Otte AP, Schermelleh L, Brockdorff N | display-authors = 6 | title = Spatial separation of Xist RNA and polycomb proteins revealed by superresolution microscopy | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 6 | pages = 2235–40 | date = February 2014 | pmid = 24469834 | pmc = 3926064 | doi = 10.1073/pnas.1312951111 | bibcode = 2014PNAS..111.2235C | doi-access = free }}</ref>

==== Mechanism ==== thumb|One super resolution study showed that Xist and PRC2 do not directly interact (above), a second study that they are tightly and statistically significantly linked. Some studies showed that PRC2 components are not associated with Xist RNA or do not interact functionally.<ref>{{cite journal | vauthors = Chu C, Zhang QC, da Rocha ST, Flynn RA, Bharadwaj M, Calabrese JM, Magnuson T, Heard E, Chang HY | display-authors = 6 | title = Systematic discovery of Xist RNA binding proteins | journal = Cell | volume = 161 | issue = 2 | pages = 404–16 | date = April 2015 | pmid = 25843628 | pmc = 4425988 | doi = 10.1016/j.cell.2015.03.025 | author-link9 = Howard Y. Chang }}</ref><ref>{{cite journal | vauthors = McHugh CA, Chen CK, Chow A, Surka CF, Tran C, McDonel P, Pandya-Jones A, Blanco M, Burghard C, Moradian A, Sweredoski MJ, Shishkin AA, Su J, Lander ES, Hess S, Plath K, Guttman M | display-authors = 6 | title = The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3 | journal = Nature | volume = 521 | issue = 7551 | pages = 232–6 | date = May 2015 | pmid = 25915022 | pmc = 4516396 | doi = 10.1038/nature14443 | bibcode = 2015Natur.521..232M }}</ref><ref>{{cite journal | vauthors = Moindrot B, Cerase A, Coker H, Masui O, Grijzenhout A, Pintacuda G, Schermelleh L, Nesterova TB, Brockdorff N | display-authors = 6 | title = A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing | journal = Cell Reports | volume = 12 | issue = 4 | pages = 562–72 | date = July 2015 | pmid = 26190105 | pmc = 4534822 | doi = 10.1016/j.celrep.2015.06.053 }}</ref><ref>{{cite journal | vauthors = Monfort A, Di Minin G, Postlmayr A, Freimann R, Arieti F, Thore S, Wutz A | title = Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells | journal = Cell Reports | volume = 12 | issue = 4 | pages = 554–61 | date = July 2015 | pmid = 26190100 | pmc = 4530576 | doi = 10.1016/j.celrep.2015.06.067 }}</ref> Another has shown, by means of mass spectrometry analysis,<ref>{{cite journal | vauthors = Minajigi A, Froberg J, Wei C, Sunwoo H, Kesner B, Colognori D, Lessing D, Payer B, Boukhali M, Haas W, Lee JT | display-authors = 6 | title = Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation | journal = Science | volume = 349 | issue = 6245 | date = July 2015 | pmid = 26089354 | pmc = 4845908 | doi = 10.1126/science.aab2276 }}</ref> that two subunits of PRC2 may interact with Xist, although these proteins are also found in other complexes and are not unique components of the PRC2 complex.

PRC2 binds the A-repeat (RepA) of Xist RNA directly and with very high affinity (dissociation constants of 10-100 nanomolar),<ref>{{cite journal | vauthors = Cifuentes-Rojas C, Hernandez AJ, Sarma K, Lee JT | title = Regulatory interactions between RNA and polycomb repressive complex 2 | journal = Molecular Cell | volume = 55 | issue = 2 | pages = 171–85 | date = July 2014 | pmid = 24882207 | pmc = 4107928 | doi = 10.1016/j.molcel.2014.05.009 }}</ref><ref>{{cite journal | vauthors = Davidovich C, Wang X, Cifuentes-Rojas C, Goodrich KJ, Gooding AR, Lee JT, Cech TR | title = Toward a consensus on the binding specificity and promiscuity of PRC2 for RNA | journal = Molecular Cell | volume = 57 | issue = 3 | pages = 552–8 | date = February 2015 | pmid = 25601759 | pmc = 4320675 | doi = 10.1016/j.molcel.2014.12.017 }}</ref> supporting Xist-mediated recruitment of PRC2 to the X chromosome. It is unclear if such interactions occurs ''in vivo'' under physiological conditions.<ref>{{cite journal | vauthors = Cerase A, Tartaglia GG | title = Long non-coding RNA-polycomb intimate rendezvous | journal = Open Biology | volume = 10 | issue = 9 | article-number = 200126 | date = September 2020 | pmid = 32898472 | pmc = 7536065 | doi = 10.1098/rsob.200126 | doi-access = free}}</ref> Failure to turn up PRC2 proteins in function screens may result from incomplete screens or because cells cannot survive or compete without PRC2. Two super-resolution microscopy analyses have presented divergent views: one showed that Xist and PRC2 are spatially separated,<ref>{{cite journal | vauthors = Cerase A, Pintacuda G, Tattermusch A, Avner P | title = Xist localization and function: new insights from multiple levels | journal = Genome Biology | volume = 16 | article-number = 166 | date = August 2015 | issue = 1 | pmid = 26282267 | pmc = 4539689 | doi = 10.1186/s13059-015-0733-y | doi-access = free }}</ref> the other that Xist and PRC2 are tightly linked.<ref>{{cite journal | vauthors = Sunwoo H, Wu JY, Lee JT | title = The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 112 | issue = 31 | pages = E4216-25 | date = August 2015 | pmid = 26195790 | pmc = 4534268 | doi = 10.1073/pnas.1503690112 | bibcode = 2015PNAS..112E4216S | doi-access = free }}</ref> Recruitment of PCR could occur through several mechanisms in parallel, including direct Xist-mediated recruitment, adaptor proteins, chromatin changes, RNA pol II exclusion, or PRC1 recruitment.<ref>{{cite journal | vauthors = Pintacuda G, Cerase A | title = X Inactivation Lessons from Differentiating Mouse Embryonic Stem Cells | journal = Stem Cell Reviews and Reports | volume = 11 | issue = 5 | pages = 699–705 | date = October 2015 | pmid = 26198263 | pmc = 4561061 | doi = 10.1007/s12015-015-9597-5 }}</ref><ref>{{cite journal | vauthors = Pinter SF | title = A Tale of Two Cities: How Xist and its partners localize to and silence the bicompartmental X | journal = Seminars in Cell & Developmental Biology | volume = 56 | pages = 19–34 | date = August 2016 | pmid = 27072488 | doi = 10.1016/j.semcdb.2016.03.023 }}</ref> For instance, PRC2 recruitment is linked to PRC1-mediated H2A119 ubiquitination in differentiating embryonic stem cells (ESCs).<ref>{{cite journal | vauthors = Almeida M, Pintacuda G, Masui O, Koseki Y, Gdula M, Cerase A, Brown D, Mould A, Innocent C, Nakayama M, Schermelleh L, Nesterova TB, Koseki H, Brockdorff N | display-authors = 6 | title = PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation | journal = Science | volume = 356 | issue = 6342 | pages = 1081–1084 | date = June 2017 | pmid = 28596365 | pmc = 6522364 | doi = 10.1126/science.aal2512 | bibcode = 2017Sci...356.1081A }}</ref><ref name="Pintacuda et al 2017">{{cite journal | vauthors = Pintacuda G, Wei G, Roustan C, Kirmizitas BA, Solcan N, Cerase A, Castello A, Mohammed S, Moindrot B, Nesterova TB, Brockdorff N | display-authors = 6 | title = hnRNPK Recruits PCGF3/5-PRC1 to the Xist RNA B-Repeat to Establish Polycomb-Mediated Chromosomal Silencing | journal = Molecular Cell | volume = 68 | issue = 5 | pages = 955–969.e10 | date = December 2017 | pmid = 29220657 | pmc = 5735038 | doi = 10.1016/j.molcel.2017.11.013 }}</ref><ref name="PYC 2017">{{cite journal | vauthors = Pintacuda G, Young AN, Cerase A | title = Function by Structure: Spotlights on Xist Long Non-coding RNA | journal = Frontiers in Molecular Biosciences | volume = 4 | article-number = 90 | date = 2017 | pmid = 29302591 | pmc = 5742192 | doi = 10.3389/fmolb.2017.00090 | doi-access = free }}</ref> where PRC1 recruitment is mediated by hnrnpK and Xist repB.<ref name="Pintacuda et al 2017" /><ref name="PYC 2017" /> In fully differentiated cells, PRC2 recruitment seems to be dependent on Xist RepA.<ref name="PYC 2017"/> Alternative and complementary pathways, such as phase separation,<ref>{{Cite bioRxiv| vauthors = Cerase A, Armaos A, Cid F, Avner P, Tartaglia GG |date=2018-06-20|title=Xist IncRNA forms silencing granules that induce heterochromatin formation and repressive complexes recruitment by phase separation |biorxiv=10.1101/351015}}</ref><ref>{{cite journal | vauthors = Cerase A, Armaos A, Neumayer C, Avner P, Guttman M, Tartaglia GG | title = Phase separation drives X-chromosome inactivation: a hypothesis | journal = Nature Structural & Molecular Biology | volume = 26 | issue = 5 | pages = 331–334 | date = May 2019 | pmid = 31061525 | doi = 10.1038/s41594-019-0223-0 | hdl = 11573/1279455 | s2cid = 146112261 | hdl-access = free }}</ref> could also be at work to establish PRC2 recruitment on the X in different experimental systems and during different stages of development. See also work from the Tartaglia lab.

== In plants == [[File:DEV035048A.jpg|thumb|The Polycomb gene FIE is expressed (blue) in unfertilised egg cells of the moss Physcomitrella patens (right) and expression ceases after fertilisation in the developing diploid sporophyte (left). In situ GUS staining of two female sex organs (archegonia) of a transgenic plant expressing a translational fusion of FIE-uidA under control of the native FIE promoter]] In ''Physcomitrella patens'' the PcG protein FIE is specifically expressed in stem cells such as the unfertilized egg cell. Soon after fertilisation the FIE gene is inactivated in the young embryo.<ref name="pmid19542356">{{cite journal | vauthors = Mosquna A, Katz A, Decker EL, Rensing SA, Reski R, Ohad N | title = Regulation of stem cell maintenance by the Polycomb protein FIE has been conserved during land plant evolution | journal = Development | volume = 136 | issue = 14 | pages = 2433–44 | date = July 2009 | pmid = 19542356 | doi = 10.1242/dev.035048 | doi-access = free }}</ref> The Polycomb gene FIE is expressed in unfertilised egg cells of the moss ''Physcomitrella patens'' and expression ceases after fertilisation in the developing diploid sporophyte.

It has been shown that unlike in mammals the PcG are necessary to keep the cells in a differentiated state. Consequently, loss of PcG causes de-differentiation and promotes embryonic development.<ref name="pmid19680533">{{cite journal | vauthors = Aichinger E, Villar CB, Farrona S, Reyes JC, Hennig L, Köhler C | title = CHD3 proteins and polycomb group proteins antagonistically determine cell identity in Arabidopsis | journal = PLOS Genetics | volume = 5 | issue = 8 | article-number = e1000605 | date = August 2009 | pmid = 19680533 | pmc = 2718830 | doi = 10.1371/journal.pgen.1000605 | doi-access = free }}</ref>

Polycomb-group proteins also intervene in the control of flowering by silencing the Flowering Locus C gene.<ref name="pmid18852898">{{cite journal | vauthors = Jiang D, Wang Y, Wang Y, He Y | title = Repression of FLOWERING LOCUS C and FLOWERING LOCUS T by the Arabidopsis Polycomb repressive complex 2 components | journal = PLOS ONE | volume = 3 | issue = 10 | article-number = e3404 | year = 2008 | pmid = 18852898 | pmc = 2561057 | doi = 10.1371/journal.pone.0003404 | bibcode = 2008PLoSO...3.3404J | doi-access = free }}</ref> This gene is a central part of the pathway that inhibits flowering in plants and its silencing during winter is suspected to be one of the main factors intervening in plant vernalization.<ref name="pmid10716723">{{cite journal | vauthors = Sheldon CC, Rouse DT, Finnegan EJ, Peacock WJ, Dennis ES | title = The molecular basis of vernalization: the central role of FLOWERING LOCUS C (FLC) | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 7 | pages = 3753–8 | date = March 2000 | pmid = 10716723 | pmc = 16312 | doi = 10.1073/pnas.060023597 | doi-access = free }}</ref>

== See also == {{Div col|colwidth=20em}} * PRC1 * PRC2 * PHC1 * PHC2 * Heterochromatin protein 1 (Cbx) * BMI1 * PCGF1, KDM2B * PCGF2 (Polycomb group RING finger protein 2) ortolog Bmi1 * RYBP * RING1 * SUV39H1 (histone-lysine N-methyltransferase) * L3mbtl2 * EZH2 (Enhancer of Zeste Homolog 2) * EED * SUZ12 (Suppressor of Zeste 12) * Jarid2 (jumonji, AT rich interactive domain 2) * RE1-silencing transcription factor (REST) * RNF2 * CBFβ * YY1 * Bivalent chromatin {{div col end}}

== References == {{reflist}}

== Further reading == {{refbegin}} * {{cite journal | vauthors = Schuettengruber B, Bourbon HM, Di Croce L, Cavalli G | title = Genome Regulation by Polycomb and Trithorax: 70 Years and Counting | journal = Cell | volume = 171 | issue = 1 | pages = 34–57 | date = September 2017 | pmid = 28938122 | doi = 10.1016/j.cell.2017.08.002 | s2cid = 43165761 | url = https://hal.archives-ouvertes.fr/hal-01596016/file/mmc3%20%281%29.pdf | doi-access = free | bibcode = 2017Cell..171...34S }} * {{cite journal | vauthors = Di Croce L, Helin K | title = Transcriptional regulation by Polycomb group proteins | journal = Nature Structural & Molecular Biology | volume = 20 | issue = 10 | pages = 1147–55 | year = 2013 | pmid = 24096405 | doi = 10.1038/nsmb.2669 | s2cid = 2681793 }} * {{cite journal | vauthors = Simon JA, Kingston RE | title = Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put | journal = Molecular Cell | volume = 49 | issue = 5 | pages = 808–24 | year = 2013 | pmid = 23473600 | pmc = 3628831 | doi = 10.1016/j.molcel.2013.02.013 }} * {{cite journal | vauthors = Golbabapour S, Majid NA, Hassandarvish P, Hajrezaie M, Abdulla MA, Hadi AH | title = Gene silencing and Polycomb group proteins: an overview of their structure, mechanisms and phylogenetics | journal = OMICS: A Journal of Integrative Biology | volume = 17 | issue = 6 | pages = 283–96 | year = 2013 | pmid = 23692361 | pmc = 3662373 | doi = 10.1089/omi.2012.0105 }} * {{cite journal | vauthors = Schwartz YB, Pirrotta V | title = Polycomb silencing mechanisms and the management of genomic programmes | journal = Nature Reviews. Genetics | volume = 8 | issue = 1 | pages = 9–22 | date = January 2007 | pmid = 17173055 | doi = 10.1038/nrg1981 | s2cid = 28227227 }} * {{cite journal | vauthors = Schuettengruber B, Chourrout D, Vervoort M, Leblanc B, Cavalli G | title = Genome regulation by polycomb and trithorax proteins | journal = Cell | volume = 128 | issue = 4 | pages = 735–45 | date = February 2007 | pmid = 17320510 | doi = 10.1016/j.cell.2007.02.009 | s2cid = 6492075 | doi-access = free | bibcode = 2007Cell..128..735S }} * {{cite journal | vauthors = Pirrotta V, Li HB | title = A view of nuclear Polycomb bodies | journal = Current Opinion in Genetics & Development | volume = 22 | issue = 2 | pages = 101–9 | year = 2012 | pmid = 22178420 | pmc = 3329586 | doi = 10.1016/j.gde.2011.11.004 }} {{refend}}

== External links == * {{cite web | url = https://www.humpath.com/spip.php?article773 | title = polycomb group proteins | publisher = Humpath.com }} * [https://www.igh.cnrs.fr/en/research/departments/genome-dynamics/chromatin-and-cell-biology/217-the-polycomb-and-trithorax The Polycomb and Trithorax page of the Cavalli lab] This page contains useful information on Polycomb and trithorax proteins, in the form of an introduction, links to published reviews, list of Polycomb and trithorax proteins, illustrative power point slides and a link to a genome browser showing the genome-wide distribution of these proteins in ''Drosophila melanogaster''. * [https://archive.today/20130417083025/http://www.evol.nw.ru/labs/lab38/spirov/hox_pro/pc.htm Drosophila Genes in Development: Polycomb-group] in the Homeobox Genes DataBase * [https://www.sdbonline.org/fly/aignfam/polycomb.htm Chromatin organization and the Polycomb and Trithorax groups] in The Interactive Fly * {{MeshName|polycomb+group+proteins}}

Category:Protein families Category:Drosophila melanogaster genes Category:Nuclear organization