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Schier, and 2006; Vastenhouw al., 2007; et transcription, al., (Bernstein these repression et poise gene or Mikkelsen to expression with thought rapid associated are for factors domains mark H3K27me3 ‘bivalent’ histone These repressive H3K4me3. contain a the to and i.e. encoding 2010; suggested genes mark modifications, al., ESCs, been et histone In have Pasini 2008). multiple regulators al., 2007; al., et al., developmental et Wang et Mikkelsen key 2008; Pasini 2010; al., 2007; et al., al., Shen et lineage et Leeb Pan 2006; 2008; al., 2007; in al., et (Boyer et ESCs) programs involved Chamberlain differentiation PRC2-deficient H3K27me3 aberrant in factors to and de-repressed leading are PRC2 key (which that specification stem repress demonstrated embryonic Shen investigating have 2008; transcriptionally studies al., and (ESCs) et Numerous EED cells (Margueron 2008). Suz12, lysine (H3K27me3) al., of H3 Ezh2, et trimethylation histone the subunits, of for core 27 responsible Ezh2 four with of RbAp48, cell (PRC2) which 2 stem composed complex adult repressive is proteins, of information, Polycomb regulation differentiation. (PcG) the and epigenetic fate for evidence group candidates repressive likely Accumulating represent Polycomb transcriptionally repair. the mediate and that homeostasis essential suggests is tissue programme differentiation for correct a of Maintenance Introduction 2. complex models process repressive knockout differentiation Polycomb these muscle and words: Using the Ezh2 Key regulate homeostasis. of not or impaired functions does repair severely Ezh2 Surprisingly, cell-type-specific muscle expand. that growth, impede and to show muscle not lineage population we did decreased the progenitor datasets, differentiation proliferative exhibited emphasise ChIP-Seq proliferation terminal the and cells critical of of RNA-Seq satellite a failure onset the profound identified isolated in the and a strains, after freshly Ezh2 to mouse Ezh2 in lacking due Ezh2-null of H3K4me3 number, Mice deletion conditional cell and essential. two stem H3K27me3 is repression reduced of of this activity and analysis regeneration maps for Ezh2 the timing genome-wide with which developmental novel together in and generated data, phase mark targets These we histone the and cells. questions, repressive but timely stem H3K27me3 these a process, the muscle in address this and differentiate To for proteins cells stem necessary (PcG) unclear. adult Polycomb-group programmes remain that for transcriptional ensure implicated the to been restriction coordinating has fate in role cell crucial of A process stepwise manner. a appropriate requires repair and generation Tissue Summary UK 9RT, SE1 London London, College Kings Medicine, Regenerative and § Cells Stem for UK ` Centre 3AT, address: CB22 *Present Cambridge, Institute, Babraham The Pugazhendhi Dhamayanthi Woodhouse*, Samuel o:10.1242/jcs.114843 doi: 565–579 126, Science Cell of Journal 2012 November 2 Accepted rsn drs:Dprmn fPamclg,Uiest fCmrde ensCutRa,CmrdeC21D UK 1PD, CB2 Cambridge Road, Court Tennis Cambridge, of University Pharmacology, of Department address: Present uhrfrcrepnec ( correspondence for Author 03 ulse yTeCmayo ilgssLtd Biologists of Company The by Published 2013. h blt osuytefnto fPC ihna dl stem adult an within PRC2 of function the study to ability The , Suz12 and hPSq z2 32m3 ucese el,PC,Stliecell Satellite PRC2, cells, stem Muscle H3K27me3, Ezh2, ChIP-Seq, Ezh2 ulebys(as ta. 95 O’Carroll 1995; al., et (Faust embryos null [email protected] ) ` arc re n enfrM Pell M. 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S.W. to BB-H019243-1 J.M.P.]. for number Research [grant funding funding Sciences the Mode studentship Responsive via J.M.P. Biological Institute, to funding and Babraham strategic competitive Biotechnology for (BBSRC) the Council thank We Funding of conflict no have they Andrews that Simon declare of authors interest. advice The and Krueger. help The Felix the and Sequencing discussions. with Tabbada. helpful performed Kristina was and by analysis Rugg-Gunn performed manuscript was Peter the sequencing to of GAIIX grateful reading are Olson We critical Eric strains. for and mice Capecchi transgenic the Mario for Tarakhovsky, Alexander thank We Acknowledgements iuino :0 o tro eprtr oehrwt AIt ae nuclei. label to Labs). DAPI with (Vector together hardset temperature Vectashield room with at mounted a h at were added 1 Cruz Slides were for These 1:300 (Invitrogen). (Santa of AF633 anti-rat dilution goat M-cadherin and AF568 specific) Technology), Technology). 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