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genome regulation by polycomb and tirthoraxprotein

genome regulation by polycomb and tirthoraxprotein
genome regulation by polycomb and tirthoraxprotein

Leading Edge

Review

Genome Regulation by Polycomb and Trithorax Proteins

Bernd Schuettengruber,1Daniel Chourrout,2,5Michel Vervoort,3,4,5Benjamin Leblanc,1and Giacomo Cavalli1,* 1Institute of Human Genetics,CNRS,141,rue de la Cardonille,34396Montpellier Cedex5,France

2Sars International Centre for Marine Molecular Biology,University of Bergen,Thormoehlensgt.55,5008Bergen,Norway

3Centre de Ge′ne′tique Mole′culaire,UPR2167CNRS,1,av.de la terrasse,91198Gif-sur-Yvette Cedex,France

4UFR de Biologie et Sciences de la Nature,Universite′Paris7,Denis Diderot,2place Jussieu,75251Paris Cedex05,France

5These authors contributed equally to this work.

*Correspondence:giacomo.cavalli@https://www.sodocs.net/doc/034960848.html,rs.fr

DOI10.1016/j.cell.2007.02.009

Polycomb group(PcG)and trithorax group(trxG)proteins are critical regulators of numerous developmental genes.To silence or activate gene expression,respectively,PcG and trxG proteins bind to speci?c regions of DNA and direct the posttranslational modi?cation of histones.Recent work suggests that PcG proteins regulate the nuclear organization of their target genes and that PcG-mediated gene silencing involves noncoding RNAs and the RNAi machinery.

Epigenetic regulation of gene expression is necessary for the correct deployment of developmental programs and for the maintenance of cell fates.Polycomb group(PcG) and trithorax group(trxG)genes were discovered in Dro-sophila melanogaster as repressors and activators of Hox genes,a set of transcription factors that specify cell identity along the anteroposterior axis of segmented ani-mals.Subsequent work has shown that PcG and trxG pro-teins form multimeric complexes that are not required to initiate the regulation of Hox genes,but rather to maintain their expression state after the initial transcriptional regu-lators disappear from the embryo.Subsequent work in Drosophila led to the identi?cation of DNA regulatory elements that recruit PcG and trxG factors to chromatin in vivo.These elements,called PcG and trxG response elements(PREs and TREs),respectively,mediate epige-netic inheritance of silent and active chromatin states throughout development(reviewed in Muller and Kassis, 2006;Schwartz and Pirrotta,2007).PcG and trxG genes have also been identi?ed in vertebrates,where they also regulate Hox genes.In addition,PcG and trxG proteins are implicated in cell proliferation(reviewed in Martinez and Cavalli,2006),stem cell identity and cancer(reviewed in Sparmann and van Lohuizen,2006;also see review by Jones&Baylin,in this issue),genomic imprinting in plants and mammals(reviewed in Delaval and Feil,2004;Guitton and Berger,2005;Bernstein et al.,in this issue)and X in-activation(reviewed in Heard,2005and Yang and Kuroda, this issue).An appreciation for the extensive biological roles for PcG and trxG proteins has motivated efforts to determine their mechanisms of action.

Some trxG and PcG components possess methyltrans-ferase activities directed toward speci?c lysines of histone H3,whereas other trxG and PcG proteins interpret these histone marks.Recent work has established the genome-wide distribution of PcG proteins,and considerable

progress has been made toward understanding how PcG and trxG proteins are recruited to chromatin and how they regulate their target genes.Here,we discuss the molecular mechanisms of action of PcG and trxG pro-teins,their roles in regulating cell fate during development in eukaryotes,and analyze their functions from an evolu-tionary perspective.

Recruitment of PcG and trxG Proteins

to Their Chromatin Targets

PcG proteins form three different classes of complexes (Table1).Polycomb repressive complex2(PRC2)con-tains the four core components:E(z)(Enhancer of zeste), Esc(Extra sex combs),Su(z)12(Suppressor of zeste12) and Nurf-55(in humans,EZH2,EED,SUZ12and RbAp46/48).The SET domain-containing E(z)subunit tri-methylates lysine27of histone H3(H3K27me3)(reviewed in Cao and Zhang,2004).This mark is speci?cally recog-nized by the chromodomain of Polycomb(Pc)(Cao and Zhang,2004),a subunit of PRC1-type complexes.PRC1 contains Pc,Polyhomeotic(Ph),Posterior sex combs (Psc)and dRing,in addition to several other components, including TBP-associated factors(Saurin et al.,2001).Re-cently,a third complex involved in homeotic gene silenc-ing,PhoRC,has been identi?ed(Klymenko et al.,2006). PhoRC includes the sequence speci?c DNA binding pro-tein Pleiohomeotic(Pho)as well as the dSfmbt protein [Scm-related gene containing four malignant brain tumor (MBT)domains],which binds speci?cally to mono-and dimethylated H3K9and H4K20via its MBT repeats.

Neither PRC2nor PRC1core complexes contain se-quence speci?c DNA binding proteins,but Pho has been shown to bind to PRC2subunits and to induce PRC2re-cruitment at the bxd PRE of the Ubx gene in Drosophila (Wang et al.,2004b).A simple pathway for PcG protein recruitment has been suggested based on the stepwise Cell128,735–745,February23,2007a2007Elsevier Inc.735

recruitment of PRC2proteins by Pho (and Pho-like,a pro-tein that binds to the same DNA motifs),followed by PRC1recruitment to the H3K27me3mark deposited by PRC2.However,PcG recruitment is much more complex than this.Firstly,Pho is not only able to recruit PRC2,but it also interacts directly with the Pc and Ph subunits of PRC1in vitro (Mohd-Sarip et al.,2002).The presence of Pho enables the core complex of PRC1(PCC)to bind speci?cally,and without the need of PRC2,to a short se-quence motif that is present at natural PREs close to Pho sites (Mohd-Sarip et al.,2005).Secondly,core PREs might be depleted of nucleosomes.Mohd-Sarip and col-leagues studied the architecture of the ternary complex of PRE DNA,Pho and PCC that had been reconstituted in vitro.This complex wraps DNA around the protein com-ponent and,in the presence of 6Pho binding sites and jux-taposed PC binding elements,it includes over 400bp of DNA in this interaction.This argues against a nucleosomal structure for this PRE in vivo (Mohd-Sarip et al.,2006).The absence of core histones at the Ubx PRE is also supported by in vivo studies using chromatin immunoprecipitation (ChIP)(Kahn et al.,2006;Mohd-Sarip et al.,2006;Papp and Muller,2006),which suggest that the H3K27me3chromatin mark might not be the recruiter of PcG proteins at core PREs.Finally,Pho binding sites alone are insuf?-cient to tether PcG proteins to DNA in vivo,even when multimerized or when the number of sites and the spacing between them is the same as in a natural PRE (Brown et al.,1998;Dejardin et al.,2005).Indeed,Pho can form a second complex with components of the INO80nucleo-some remodeling complex,and may play other roles in addition to recruitment of PcG proteins,which may be mediated by a subset of the genomic Pho binding sites (Klymenko et al.,2006).Moreover,a Drosophila mutant lacking both Pho and Pho-like is lethal at a late develop-mental stage and,in mutant salivary glands,most PcG sites are stained normally in polytene chromosomes de-spite lack of detectable Pho protein (Brown et al.,2003),suggesting that other proteins can recruit PcG factors in the absence of Pho and Pho-like.GAGA factor (GAF),Pip-squeak,Dsp1,Grainyhead and members of the Sp1/KLF family have all been suggested to be involved in PcG re-cruitment (reviewed in Muller and Kassis,2006).Mutations in these genes do not have a clear PcG phenotype and,in-triguingly,all seem to be involved in activation as well as in silencing.One possibility is that a combination of several DNA binding factors,including as yet unknown compo-nents,could lead to tethering of PcG proteins to DNA in vivo.

To date,PREs have only been characterized in Dro-sophila .In general,PREs can be simply de?ned as DNA elements necessary and suf?cient for recruitment of PcG complexes and for PcG-dependent silencing of ?anking promoters.Many of the PcG binding sites identi?ed by chromatin immunoprecipitation in vertebrates might ?t this criterion,and this prediction will be tested by trans-genic assays.Their DNA sequences are likely to differ from ?y PREs,because three of the DNA binding factors

Table 1.PcG and trxG Complexes

Drosophila melanogaster

Human

PcG complexes PhoRC

dSfmbt ?Pho

?PRC2

E(z)EZH2Esc EED Su(z)12SUZ12N55

RpAp48RpAp46

PRC1

dRing RING1A Pc HPC1-3Ph HPH1-3Psc BMI1Scm

SCMH1-2TBP-associated factors

trxG complexes SWI/SNF

Brm BRM Osa BAF250Moira BAF170Snr1

BAF47NURF

Iswi SNF2L N38?N301BPTF N55

RpAp46RpAp48TAC1

Trx a dCBP Sbf1

Ash1

Ash1dCBP

MLL1-3

MLL1-3a WDR5ASH2L RbBP5CFP1

Only the core components of each complex are shown.a

Trx is an ortholog of MLL proteins,but the TAC1complex isolated in Drosophila is composed of proteins that differ from the subunits of the MLL complex.However,orthologs of the mammalian MLL core-complex subunits are present in the Drosophila genome,and therefore MLL-like complexes may exist in ?ies.Question mark indicates that the protein is present in human,but it is not known whether it forms the same complex as in ?ies.

736Cell 128,735–745,February 23,2007a2007Elsevier Inc.

involved in PcG recruitment,GAF,Pipsqueak and Zeste, are not conserved in vertebrates.

In addition to a‘‘DNA code’’and,possibly,the H3K27me3mark,small RNAs and proteins of the RNAi machinery might be involved in PcG recruitment.It was shown that silencing mediated by a3.6kilobase DNA ele-ment from the Fab-7regulatory region of the Abd-B Hox gene was relieved by mutations in the RNAi machinery (Grimaud et al.,2006).Although the recruitment of PcG proteins was only slightly affected(suggesting that RNAi-independent mechanisms are suf?cient to anchor PcG complexes at a majority of their endogenous target genes) a recent report shows that the human AGO1homolog can drive transcriptional gene silencing of promoters targeted by speci?c small interfering RNAs(siRNAs)via recruitment of the PcG protein EZH2(Kim et al.,2006).However,the reported phenotypes caused by mutations in genes of the RNAi machinery are not similar to those seen in PcG mutants.Thus,RNAi components might act redundantly with DNA binding proteins at a subset of the PcG targets. Recruitment of trxG proteins is even more mysterious. TrxG proteins are a somewhat heterogeneous group (Table1).One class of trxG members is composed of SET domain factors like Drosophila Trx and Ash1and vertebrate MLL,as well as their associated proteins.A second class of trxG factors includes components of ATP-dependent chromatin remodeling complexes like the SWI/SNF or the NURF complexes.Vertebrate com-plexes containing homologs of Drosophila Trx and Ash1 proteins are recruited at Hox genes,but the mechanisms are unknown(Hughes et al.,2004;Wysocka et al.,2003). In Drosophila,Trx binds a minimal Fab-7element in sali-vary glands in the absence of transcriptional activation (Dejardin and Cavalli,2004).Other work suggests that a second DNA element overlapping the bxd PRE up-stream of Ubx is involved in Trx-dependent maintenance of Ubx activation(Tillib et al.,1999).Furthermore,Trx is reported to bind at this element irrespective of the state of Ubx expression in imaginal discs of Drosophila larvae (Papp and Muller,2006),suggesting that speci?c DNA tethers recruit Trx independent of the action of transcrip-tion factors.In Drosophila embryos,Trx is observed to constitutively bind to the promoter regions of the Ubx gene and of the bxd element.Interestingly however,this paper also reports recruitment of Trx to transcribed Ubx regions,but only upon activation(Petruk et al.,2006). Thus,between the two papers there is a discrepancy in Trx location.However,the?rst study used antibodies di-rected against the C-terminal part of the protein,whereas in the latter study the antibody was directed against the N-terminal part.The Trx protein is proteolytically cleaved by the Taspase enzyme(Hsieh et al.,2003),and the two moieties might target different chromatin regions upon cleavage.

Other trxG components seem to be recruited to chro-matin in an activation-dependent manner.For instance, upon Ubx activation Ash1is recruited to the region imme-diately downstream the transcription start site(Papp and

Muller,2006).The SWI/SNF component Brm is also re-cruited to polytene chromosomes upon activation of a transgene carrying a minimal Fab-7element(Dejardin and Cavalli,2004).Interestingly,mutation of Zeste sites in the Fab-7element prevents recruitment of Brm,but not of Trx.Thus,multiple DNA tethers cooperate for recruitment of trxG proteins needed for gene activation.

In summary,recruitment of PcG and trxG proteins in-volves combinatorial signals from multiple DNA motifs. The simultaneous binding of multiple silencing and acti-vating factors at PREs/TREs suggests that they build switchable regulatory platforms(Figure1),which may be able to read early developmental cues and transform them into heritable states of gene expression or transcrip-tional silencing.

Posttranslational Chromatin Marks Linked

to PcG and trxG Proteins

PRC2-type complexes possess H3K27-speci?c trimethy-lase activity(Cao and Zhang,2004)whereas several trxG complexes have H3K4trimethylase activity(Figure2A). (Byrd and Shearn,2003;Dou et al.,2005;Wysocka et al.,2005).Do these two histone trimethylation marks mediate PcG-dependent silencing and trxG-dependent activation as part of a Yin and Yang relationship?

Recent genome-wide analysis of the distribution of both marks reveals insight into their epigenetic roles.The com-ponents of the PRC2complex in?ies,mouse and human are typically found in the regions that are trimethylated at H3K27(Boyer et al.,2006;Lee et al.,2006;Schwartz et al., 2006;Tolhuis et al.,2006).In contrast,H3K4me3is pres-ent at most active promoters in the genome(Kim et al., 2005and see review by Li et al.in this issue).

Papp and Mu¨ller analyzed the relation between H3K4me3and H3K27me3at the Drosophila Ubx gene by ChIP analysis of tissues in which the gene is in an active or a repressed state(Papp and Muller,2006).Both Trx and PcG proteins bind at the Ubx PREs in either state without extensive coating of the remainder of Ubx chromatin.Yet, in the repressed state,the whole Ubx gene is trimethylated at H3K27.In contrast,in the active state,H3K27me3is still present in the upstream region of the gene,but is virtually absent at the promoter and the coding region of the gene. The absence of H3K27trimethylation in part of the gene correlates with the binding of Ash1immediately down-stream to the promoter,which induces trimethylation of H3K4.Trx binds constitutively at the PRE in the absence of detectable H3K4me3around the PRE region(as re-vealed by an antibody directed against the C-terminal portion of the protein).The mammalian Trx homolog MLL1is also responsible for H3K4trimethylation at the human HOXA9locus(Dou et al.,2005),but a knockout of the SET domain of mouse Mll results in the speci?c de-pletion of monomethylated H3K4(Terranova et al.,2006) at the Hoxd4and Hoxc8genes.Thus,the role of Trx and MLL1in histone methylation might be gene speci?c and might be assisted by additional histone methylase Cell128,735–745,February23,2007a2007Elsevier Inc.737

activities to produce the H3K4me3mark associated with gene expression.

Additional components might also be involved in H3K4 trimethylation.In yeast,H3K4trimethylation requires monoubiquitylation of histone H2B at lysine123by Rad6/Bre1(Sun and Allis,2002).Although Drosophila dBre1has no known involvement in trxG-mediated activa-tion,a complex between the proteins USP7and GMP synthetase(GMPS)has been shown to contribute to PcG-mediated gene silencing via deubiquitylation of histone H2B(van der Knaap et al.,2005).This suggests a trans-histone interplay between activating H3K4trimethylation,stimulated by ubiquitylation of H2B,and silencing H3K27 trimethylation,stimulated by deubiquitylation of H2B (Figure2B).

In addition to H3K27trimethylation,PRC2containing a speci?c isoform of the EED protein is thought to catalyze trimethylation of lysine26of histone H1(H1K26me3) (Kuzmichev et al.,2004).Surprisingly,similar experiments performed with recombinant complexes and di-or oligo-nucleosomes could not con?rm whether it has the ability to methylate histone H1(Martin et al.,2006),suggesting that differences in assay conditions can affect the histone substrate speci?city of PRC2-type

complexes.

Figure2.Histone Marks in PcG and trxG

Protein Function

(A)PcG and trxG complexes deposit histone

marks that play complementary roles in silenc-

ing and activation of their target chromatin.

The enzymatic subunits of PcG and trxG

complexes responsible for H3K27me3and

H3K4me3,respectively,in?ies and humans

are shown.

(B)Ubiquitylation of histone H2B on lysine K123

(H2BK123ub1)by the yeast complex Rad6/

Bre1stimulates histone methylation of histone

H3on lysine4by COMPASS,a trxG complex,

resulting in gene activation.In contrast,deubi-

quitylation of histone H2B by the Drosophila

USP7/GMPS complex may be essential for

histone methylation of histone H3on lysine

27(H3K27me3).Moreover,this methyl mark

might help to recruit dRing,a protein with E3

ligase activity leading to ubiquitylation of his-

tone H2A on lysine119

(H2AK119ub1).

Figure1.PREs and TREs as Molecular

Binding Platforms

Multiple DNA binding proteins like Pho(P),

Dsp1(D),SP1/KLF(S),Zeste(Z),GAGA factor

(G),Pipsqueak(PQ),and Grainyhead(G)recruit

PcG complexes to PREs.The recruitment of ei-

ther PcG or TrxG proteins to the PRE sequence

does not depend on the activation status of the

gene.Moreover,general transcription and

elongation factors,such as TBP and Spt5,are

constitutively bound to the PRE.A develop-

mental signal then determines whether the

PRE mediates gene activation or gene repres-

sion,which are accompanied by trimethylation

(Me)of histone H3on lysine4or lysine27,re-

spectively.Upon activation,Kismet(Kis),a pro-

tein facilitating elongation,and Ash1,leading to

local H3K4methylation,are recruited to the

promoter region.Small RNAs(red ladder)may

also contribute to PcG protein recruitment. 738Cell128,735–745,February23,2007a2007Elsevier Inc.

PcG complexes of the PRC1-type also contain an evolutionarily conserved histone modi?cation activity leading to ubiquitylation of lysine119of histone H2A (H2AK119ub1,see Figure2B)(de Napoles et al.,2004; Wang et al.,2004a),which is required for PcG-mediated silencing of the Drosophila Ubx gene(Wang et al., 2004a)as well as of the mouse HoxC13gene(Cao et al., 2005).A putative‘‘reader’’of this histone mark remains to be identi?ed.Other histone modi?cations are associ-ated with PcG and trxG proteins,although their role is not well understood.For instance,Papp and colleagues reported that trimethyhlation of H3K9and H4K20accom-panies the H3K27me3mark(Papp and Muller,2006). Mechanisms of trxG-Mediated Activation

and PcG-Mediated Silencing

What are the roles of all these histone modi?cations and are they suf?cient to explain PcG-mediated silencing and trxG-mediated activation?H3K4me3is recognized by the PHD?nger domain of the Nurf-301protein(Li et al.,2006;Wysocka et al.,2006).The NURF complex tethered to trxG responsive promoters might facilitate the recruitment of the transcriptional machinery via ATP-dependent nucleosome remodeling.H3K4me3might also stimulate transcriptional elongation.In particular, H3K4me3and Ash1are found downstream to the Ubx promoter(Papp and Muller,2006).Trx has also been shown to facilitate transcriptional elongation at heat shock genes(Smith et al.,2004)and,more recently,the Dro-sophila Trithorax complex TAC1has been proposed to play a global role in transcriptional elongation(Petruk et al.,2006).Mll,the mouse counterpart of Trx,is also dis-tributed all along the coding part of its Hox target genes, and Mll mutations affect the distribution of elongating RNA pol II(Milne et al.,2005).

What then is the role of H3K27me3?PRC2-type com-plexes are conserved throughout the eukaryotic king-doms,including in those organisms with no trace of PRC1,such as plants.A plant homolog of E(z)deposits the H3K27me3mark on large domains spanning its target genes leading to their silencing(Schubert et al.,2006).It is not clear how silencing in the absence of PRC1is achieved.One possibility is that PRC1is replaced by other factors.For instance,the LIKE HETEROCHROMATIN

PROTEIN1(LHP1)is necessary for the maintenance of the epigenetically repressed state of some euchromatic genes(Sung et al.,2006).An alternative possibility is that H3K27me3represses transcription directly,for in-stance by inhibiting some step involved in transcriptional activation or by preventing the deposition of histone marks associated with gene activation,such as acetyla-tion,ubiquitylation of histone H2B or trimethylation of H3K4(Figure3A).

Another notable feature of H3K27trimethylation is that it is distributed over large chromosomal domains,some-times covering several hundreds of kilobases.This might provide the basis for epigenetic inheritance of PcG-de-pendent silencing during cell division.Even if PcG proteins

are lost from their targets during DNA replication or mitosis (Buchenau et al.,1998),they would rapidly gain access to the originally silenced chromatin via speci?c interactions with PRE DNA,assisted by interaction of the Pc chromo-domain with H3K27me3.Meanwhile,the same mark might prevent the local deposition of activating marks and inap-propriate gene reactivation.Binding of PRC2components to PREs would rapidly restore the trimethylation of H3K27 that is lost upon DNA replication.

Although histone marks may be directly responsible for PcG-mediated repression,it is important to note that some PcG target genes must be strongly and reliably repressed throughout many cell divisions.This robust silencing might require the contribution of

other Figure3.Different Layers of PcG-Mediated Gene Silencing

(A)PRC2-mediated histone H3methylation on lysine27(Me)might

directly interfere with transcriptional activation and/or inhibit ubiquity-lation of histone H2B or trimethylation of H3on lysine4.Transcription of noncoding RNAs may mediate repression of a downstream gene by transcriptional interference.TAFs,TBP-associated factors.

(B)H3K27me3and PRC1complexes spread from the PRE to a pro-

moter located close to the PRE,interfering with ATP-dependent nucle-osome remodeling activities(SWI/SNF)and RNA Pol II recruitment.

The E3ligase activity of dRing leads to H2A ubiquitylation,contributing to silencing by unknown mechanisms.

(C)RNA Pol II can be recruited to a subset of PcG-silenced genes,sug-

gesting a role for PRC1in gene silencing downstream of RNA Pol II assembly at the promoter region.For promoters located far away from PRE sequences,PRC2complexes bound at PREs may loop out and contact neighboring nucleosomes.E(z)activity may then gen-erate a large repressive domain of H3K27me3.Moreover,PRE looping may allow PcG proteins to contact distant promoters.

Cell128,735–745,February23,2007a2007Elsevier Inc.739

mechanisms in addition to the marking of histones.PRC1 can repress ATP-dependent nucleosome remodeling by the SWI/SNF complex in vitro(Shao et al.,1999),and the PCC complex is able to condense chromatin in a Psc-dependent manner and in the absence of histone modi?-cations(Figure3B)(Francis et al.,2004).Moreover,native PRC1in Drosophila contains TBP-associated factors (Breiling et al.,2001;Saurin et al.,2001),suggesting that PcG proteins might contact promoters.Consistent with this notion,PRE-mediated silencing does not necessarily prohibit recruitment of RNA pol II,but may interfere with DNA-melting at the promoter during initiation of transcrip-tion(Dellino et al.,2004).

The position of PREs relative to their target genes is vari-able.Sometimes they overlap the promoter,whereas in other cases they are located tens of kilobases away (Negre et al.,2006).One possible explanation for silencing of distant promoters is that PRE-bound E(z)establishes a large domain of H3K27me3via transient chromatin con-tacts mediated by the looping of PREs.This mark might then silence promoters located within its realm.Alterna-tively,PcG proteins bound to a PRE might establish spe-ci?c contacts with promoter-bound components of the transcription machinery upon PRE looping(Figure3C). Contact between distal domains by PRE looping has been demonstrated by the tethering of Dam methyltrans-ferase to the Drosophila Fab-7region(Cleard et al.,2006). Moreover,a recent study(in this case,using a transgenic construct containing the PRE upstream of Ubx)indicates that PRE looping can drive promoter silencing(Comet et al.,2006).This is also consistent with the weak but sig-ni?cant binding of PcG members to the Ubx promoter in Drosophila embryos or cultured cells(Comet et al.,2006; Kahn et al.,2006).

Noncoding RNAs(ncRNAs)may also play a role in the function of PcG and trxG proteins,but studies have pro-duced contrasting results.It had been suggested from earlier work that ncRNAs produced from the regulatory regions of Hox genes may counteract PcG-dependent silencing(reviewed in Schmitt and Paro,2006).Further ev-idence for an activating role of ncRNAs came from a study of the bxd regulatory region of the Ubx gene,in which bxd transcripts are shown to recruit the Ash1protein to this re-gion inducing Ubx transcription in larval tissues(Sanchez-Elsner et al.,2006).However,these results contrast with more recent work showing that in embryos,Ubx is not transcribed in the same cells as bxd,and that embryonic bxd transcripts may participate in PcG-mediated silencing rather than activation of Ubx(Petruk et al.,2006).In partic-ular,the authors did not observe ectopic activation of Ubx by overexpression of bxd transcripts in larval tissues.They further showed that repression of Ubx by bxd transcription is mediated in cis by transcriptional interference(Fig-ure3A),and does not involve siRNA or miRNA-based mechanisms.Also,bxd ncRNAs were not detected in lar-val stages(Petruk et al.,2006),making it unlikely that they are involved in the maintenance of repression.It will be es-sential to examine the distribution of PcG proteins at the Ubx gene with or without bxd transcription to clarify whether transcription at the bxd region displaces PcG components.In summary,ncRNAs are likely to play a role in regulating PcG silencing at a subset of the target genes,but more work is required in order to clarify their function and understand their molecular mechanisms of action.

The formation of subnuclear silencing compartments might also contribute to the stable repression of transcrip-tion.Drosophila PcG proteins have a speckled nuclear distribution(Grimaud et al.,2006)and the number of ‘‘PcG bodies’’is progressively reduced during develop-ment,and is smaller than the number of genomic binding sites detected by combining ChIP with DNA microarrays (ChIP on chip)(Schwartz et al.,2006;Tolhuis et al., 2006).A combination of immuno?uorescence staining with DNA FISH has shown that multiple target PcG ele-ments can associate in the nucleus to enhance the strength of PcG-mediated silencing(Bantignies et al., 2003).Clustering of PcG target genes into PcG bodies might facilitate silencing by exclusion of RNA polymerase. Interestingly,the association of PcG target elements re-quires nuclear components of the RNAi machinery that colocalize with PcG proteins(Grimaud et al.,2006).

In mammalian cells PcG-mediated repression and DNA methylation might be coordinated in order to stabilize si-lencing at PcG target genes.EZH2can directly recruit DNA methyltransferases(DNMTs)to target genes(Rey-nolds et al.,2006;Vire et al.,2005),and it collaborates with DNMT1to recruit Bmi-1to PcG bodies(Hernandez-Munoz et al.,2005b).Two recent studies show that Polycomb-marked genes are major targets for DNA methyltransferases,leading to de novo methylation of PcG target genes and to aberrant and permanent silenc-ing in cancer cells(Schlesinger et al.,2006;Widsch-wendter et al.,2006).Additional work is needed to under-stand what triggers PRC2-mediated recruitment of DNA methyltransferases during tumorigenesis.

These data indicate that the balance between gene si-lencing and transcriptional activation at PcG/trxG target genes is regulated by direct interactions with the tran-scriptional machinery,the deposition of speci?c epige-netic marks on histones and DNA,the transcription of non-coding RNA,and the regulation of nuclear organization. Genome-Wide Distribution and Biological Functions of PcG Proteins

The genome-wide distributions of PcG proteins have been described recently in mouse and human cells and in Dro-sophila.Although the comparison is not straightforward because different cell types and PcG proteins were ana-lyzed,these studies clearly indicate important similarities as well as differences between vertebrates and?ies.In all species,binding of PcG proteins is highly correlated with the distribution of the H3K27me3mark,which is sometimes localized to restricted genomic regions, whereas in other cases it forms domains that are hundreds of kilobases in size,the largest ones including Hox gene

740Cell128,735–745,February23,2007a2007Elsevier Inc.

clusters(Boyer et al.,2006;Bracken et al.,2006;Lee et al., 2006;Negre et al.,2006;Schwartz et al.,2006;Squazzo et al.,2006;Tolhuis et al.,2006).PcG binding negatively correlates with the presence of RNA pol II,suggesting that RNA pol II is excluded from many PcG target genes as a consequence of silencing.A striking observation common to all reports is that PcG proteins bind preferen-tially to genes encoding transcription factors,including many homeodomain-containing genes.This suggests that the main function of PcG proteins is to regulate tran-scription pathways.Meta-analysis of the putative target genes from these studies reveals that many of the target genes are common in the three species analyzed.As an example,98of the260target genes identi?ed by Schwartz and coworkers have clear mouse and human homologs(identi?ed by HomoloGene).Only26of them are unique targets in?ies,whereas the72others are tar-gets in human and/or mouse(Figure S1A in the Supple-mental Data available with this article online).Strikingly, 63of these72conserved target genes(87.4%)encode transcription factors,while only38.5%of the noncon-served targets do(Figures S1B and S1C;Tables S1and S2).Clearly,genes encoding transcription factors repre-sent the most highly conserved class of PcG targets. This indicates that regulation of transcriptional pathways is a major raison d’e?tre of PcG genes.

Many of the PcG target genes are involved in develop-mental patterning,morphogenesis,and organogenesis. Some of these pathways are highly enriched in PcG tar-gets.For instance,55%of the transcription factors known to be involved in segmentation of the?y embryo were scored as PcG targets in several independent mapping studies(Figure S2A;Table S3).Similarly,most of the mas-ter transcription regulatory genes involved in eye and limb development are bound by PcG proteins(Figures S2B, S2C,and S3).This suggests that PcG proteins might play a global role to orchestrate these pathways.Future work should show how many of these targets are bound in each cell type and how many bound genes are indeed regulated by these proteins.

Despite similarities in the biochemistry of PcG com-plexes and in the identity of target genes,striking differ-ences in the distribution of PcG components were also found.Mouse and human PRC2components bind throughout the H3K27me3regions(Bracken et al.,2006; Lee et al.,2006;Squazzo et al.,2006),whereas Drosophila PRC2members bind to restricted regions,presumably PREs,even though H3K27me3covers large domains (Papp and Muller,2006;Schwartz et al.,2006).Thus,the molecular mechanisms by which H3K27me3is deposited on chromatin might differ between?ies and vertebrates. Furthermore,over90%of the mammalian PcG binding sites are located close to proximal gene promoter ele-ments(Boyer et al.,2006;Lee et al.,2006),which is much higher than in Drosophila(Negre et al.,2006),sug-gesting that?y PcG proteins frequently act over a longer range than in mammals.Finally,although the binding of ?y PcG proteins shows some degree of developmental

dynamics,many?y target sites are constitutively bound throughout development(Negre et al.,2006).Binding of PcG proteins to their target genes in vertebrates appears more dynamic,and many of the PcG targets in embryonic stem cells are activated at later stages,concomitant with loss of PcG proteins(Boyer et al.,2006;Lee et al.,2006). This suggests that,although?y PcG proteins may be used for epigenetic maintenance of transcriptional states at many targets,mammalian PcG factors are often involved in reversible gene repression,and other systems such as DNA methylation might stably lock in transcriptional si-lencing in these organisms.This is consistent with the high levels of PcG gene expression and a prominent role of PcG proteins in maintenance of stem cell identity in mammals and it indicates that PcG(and probably trxG) factors do not only serve to maintain long term memory of transcriptional states.

Evolution of PcG and trxG Genes

These observations put into question some preconceived views of the biological role of PcG and trxG proteins and suggest that the analysis of these factors from an evolu-tionary perspective might give useful insight into their function.PcG and trxG proteins are often said to be evo-lutionarily conserved.Indeed,most trxG components are found in fungi,plants and animals(Supplemental Experi-mental Procedures;Table S4),consistent with a con-served role in the regulation of global gene transcription.

The components of the PRC2complex are found in plants and animals,but not in the distantly-related fungi Saccharomyces cerevisiae and Schizosaccharomyces pombe(Figure4).However,their ancient origin is con-?rmed by their presence in another fungus,Neurospora crassa,which also possesses the H3K27me3mark(Eric Selker,personal communication).Thus,PRC2genes might have an ancient function in transcriptional repres-sion.

The picture is much more complex for components of PRC1.First,there is no trace of the core PRC1genes in fungi and plants(Figure4)(Springer et al.,2002).Blast analysis of several recently sequenced animal genomes (Supplemental Experimental Procedures)revealed that PRC1genes originated early in animal evolution.They are present in‘basal’animals:two different cnidarian spe-cies(Hydra magnipapillata and Nematostella vectensis) and,at least to some extent,in the sponge Reniera sp. (Figure4).The PRC1gene set is complete in several insect and vertebrate species,as well as in the echinoderm Strongylocentrotus purpuratus,but a varying number of PRC1genes are missing in species from other phyla(Fig-ure4).For instance,all PRC1core genes(except Scm)are absent in two Caenorhabditis species,and at least three PRC1subunits are not found in the urochordate Oiko-pleura dioica.Finally,Polycomb itself,the‘‘reader’’of the H3K27me3histone mark,is missing in many species though present in both cnidarians(Figure4).This is a strong indication that PRC1genes have been repeatedly lost during evolution of the animal kingdom.

Cell128,735–745,February23,2007a2007Elsevier Inc.741

The phenotypes of PcG mutants and the strong binding of PRC1to Hox gene clusters in ?ies and vertebrates sug-gest that these clusters are important PRC1targets.Thus,one hypothesis might be that PRC1genes can be lost as a consequence of the disintegration of the Hox gene clus-ter,which occurred repeatedly during evolution (Chourr-out et al.,2006;Pierce et al.,2005;Seo et al.,2004).In-deed,most PRC1genes are absent in the urochordate Oikopleura dioica ,which is an extreme example due to its nine unlinked Hox genes (Seo et al.,2004).PRC1genes are also absent in both Caenorhabditis species,which have profoundly rearranged Hox clusters (Aboobaker and Blaxter,2003).However,the integrity of Hox gene clusters does not strictly correlate with the presence of a full set of PRC1genes (Figure 4).Indeed,most or all PRC1genes are found in several species with degener-ated clusters,including both cnidarians Nematostella vec-tensis and Hydra magnipapillata (Chourrout et al.,2006)the platyhelminth Schistosoma mansonii (Pierce et al.,2005)and the urochordate Ciona intestinalis (Spagnuolo

et al.,2003).It is important to stress that the function of Hox genes is essentially unknown in most animal species apart from arthropods/vertebrates.In other species,these genes may not necessarily specify the anteroposterior axis of the body plan.However,diminution of the PRC1complement may accompany breakdown of the Hox clus-ter without being caused by it.Elucidating how PcG has coevolved with the Hox cluster could illuminate the con-tribution of epigenetic mechanisms to the evolution of animal development.

An interesting hypothesis is that the role of PRC1pro-teins in mammalian stem cells might re?ect an evolution-arily conserved function for these factors in regulating cell plasticity and/or switching between pluripotent and differentiated cell states.PRC1genes may be absolutely required in species showing strong cellular plasticity and a developmental regulation including the ability to regen-erate up to the adult stage,as observed in cnidarians.In these species,PRC1might cooperate with PRC2and trxG complexes to reinforce and ?ne-tune silencing

of

Figure 4.Phylogenetic Distribution of the PRC1,PRC2,and Hox Gene Clusters

Depicted is a current view of the phylogenetic relationships among a broad spectrum of eukaryotes (Adoutte et al.,2000;Delsuc et al.,2006;Kurtzman and Robnett,2003).Phylogenetic groups are indicated either on the left of the nodes that de?ne each group or below some of the terminal branches.For each species,+indicates the presence and àthe absence of the proteins that constitute the PRC1and PRC2complexes.The existence of Hox gene clusters in the different species is also indicated.+indicates the presence of one or more ‘‘bona ?de’’Hox clusters,+/àindicates the existence of partial Hox clusters,–indicates that Hox genes exist,but are not clustered,and X indicates the absence of Hox genes.

742Cell 128,735–745,February 23,2007a2007Elsevier Inc.

master developmental genes involved in these functions. Conversely,PRC1genes—in particular Pc—would not be required in animals displaying highly determinate development with invariant cell lineage such as Caeno-rhabditis and the urochordates.In these cases the differ-ential rates of genome evolution might have resulted in variable levels of PRC1gene loss and breakdown of Hox gene clusters within each major taxon.

Perspectives

Thanks to recent fundamental discoveries and the devel-opment of analytical tools,we are likely to witness great progress in the coming years toward understanding the biological roles of PcG and trxG proteins.This will include clarifying the role of histone marks in PcG and trxG regu-lation.Furthermore,the activities of PcG and trxG com-plexes toward nonhistone substrates have not been inves-tigated in detail.For instance,human Pc2/CBX4has been shown to have SUMO E3activity directed toward CtBP, a transcriptional corepressor(Kagey et al.,2005).PcG and trxG proteins are themselves among the putative non-histone targets.For example,BMI1can be ubiquitylated by the CULLIN3/SPOP E3ligase to contribute to female X-inactivation(Hernandez-Munoz et al.,2005a).The set of rules that lead to the targeting of speci?c genes by PcG and trxG proteins should also be decrypted.In partic-ular,we need to learn more about the contribution of nu-clear organization and RNAi components.Another excit-ing area of investigation will be to determine how these proteins transmit memory of gene expression states dur-ing the process of cell division.To date this long-standing question has not been approached directly and address-ing it might require new technology.Finally,genomic and proteomic studies,evolutionary analysis using bioinfor-matics,and experimental approaches in nonmodel organ-isms will provide new insights into the biological roles of these proteins.

Supplemental Data

Supplemental Data include Supplemental Experimental Procedures, Supplemental References,three?gures,and four tables and can be found with this article online at https://www.sodocs.net/doc/034960848.html,/cgi/content/full/ 128/4/735/DC1/.

ACKNOWLEDGMENTS

We thank E.Zuckerkandl for initial discussion on PcG evolution,and E.Selker for sharing unpublished data.We thank the DoE-JGI and D.Rokhsar(Nematostella and Reniera Genome projects),the J.Craig Venter Institute,and the National Human Genome Research Institute (Hydra Genome Project)for public access to assembled and nonas-sembled genome data.The Oikopleura genome was sequenced by Genoscope in collaboration with the Sars Centre.B.S.is supported by the Austrian Fonds zur Fo¨rderung der wissenscha?ichen Forschung;M.V.by the CNRS and by the Ministe`re Franc?ais de la Recherche through the ACI Jeunes chercheurs et jeunes chercheuses.

G.C.is supported by the CNRS,the HFSPO,the European Union FP6 (Network of Excellence‘‘The Epigenome’’and STREP‘‘3D Genome’’), the Ministe`re Franc?ais de la Recherche(ACI BCMS2004),and by the Agence Nationale pour la Recherche(ANR-3D Epigenome).

REFERENCES

Aboobaker,A.,and Blaxter,M.(2003).Hox gene evolution in nema-todes:novelty conserved.Curr.Opin.Genet.Dev.13,593–598.

Adoutte,A.,Balavoine,G.,Lartillot,N.,Lespinet,O.,Prud’homme,B., and de Rosa,R.(2000).The new animal phylogeny:reliability and https://www.sodocs.net/doc/034960848.html,A97,4453–4456.

Bantignies,F.,Grimaud,C.,Lavrov,S.,Gabut,M.,and Cavalli,G.

(2003).Inheritance of Polycomb-dependent chromosomal interactions in Drosophila.Genes Dev.17,2406–2420.

Boyer,L.A.,Plath,K.,Zeitlinger,J.,Brambrink,T.,Medeiros,L.A.,Lee, T.I.,Levine,S.S.,Wernig,M.,Tajonar,A.,Ray,M.K.,et al.(2006).Poly-comb complexes repress developmental regulators in murine embry-onic stem cells.Nature441,349–353.

Bracken,A.P.,Dietrich,N.,Pasini,D.,Hansen,K.H.,and Helin,K.

(2006).Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions.Genes Dev.20,1123–1136.

Breiling,A.,Turner,B.M.,Bianchi,M.E.,and Orlando,V.(2001).Gen-eral transcription factors bind promoters repressed by Polycomb group proteins.Nature412,651–655.

Brown,J.L.,Fritsch,C.,Mueller,J.,and Kassis,J.A.(2003).The Dro-sophila pho-like gene encodes a YY1-related DNA binding protein that is redundant with pleiohomeotic in homeotic gene silencing.

Development130,285–294.

Brown,J.L.,Mucci,D.,Whiteley,M.,Dirksen,M.L.,and Kassis,J.A.

(1998).The Drosophila Polycomb group gene pleiohomeotic encodes

a DNA binding protein with homology to the transcription factor YY1.

Mol.Cell1,1057–1064.

Buchenau,P.,Hodgson,J.,Strutt,H.,and Arndt-Jovin,D.J.(1998).

The distribution of polycomb-group proteins during cell division and development in Drosophila embryos:impact on models for silencing.

J.Cell Biol.141,469–481.

Byrd,K.N.,and Shearn,A.(2003).ASH1,a Drosophila trithorax group protein,is required for methylation of lysine4residues on histone H3.

https://www.sodocs.net/doc/034960848.html,A100,11535–11540.

Cao,R.,Tsukada,Y.I.,and Zhang,Y.(2005).Role of Bmi-1and Ring1A in H2A Ubiquitylation and Hox Gene Silencing.Mol.Cell20,845–854.

Cao,R.,and Zhang,Y.(2004).The functions of E(Z)/EZH2-mediated methylation of lysine27in histone H3.Curr.Opin.Genet.Dev.14, 155–164.

Chourrout,D.,Delsuc,F.,Chourrout,P.,Edvardsen,R.B.,Rentzsch,

F.,Renfer,E.,Jensen,M.F.,Zhu,B.,de Jong,P.,Steele,R.E.,and

Technau,U.(2006).Minimal ProtoHox cluster inferred from bilaterian and cnidarian Hox complements.Nature442,684–687.

Cleard,F.,Moshkin,Y.,Karch,F.,and Maeda,R.K.(2006).Probing long-distance regulatory interactions in the Drosophila melanogaster bithorax complex using Dam identi?cation.Nat.Genet.38,931–935.

Comet,I.,Savitskaya,E.,Schuettengruber,B.,Negre,N.,Lavrov,S., Parshikov,A.,Juge,F.,Gracheva,E.,Georgiev,P.,and Cavalli,G.

(2006).PRE-Mediated Bypass of Two Su(Hw)Insulators Targets PcG Proteins to a Downstream Promoter.Dev.Cell11,117–124.

de Napoles,M.,Mermoud,J.E.,Wakao,R.,Tang,Y.A.,Endoh,M., Appanah,R.,Nesterova,T.B.,Silva,J.,Otte,A.P.,Vidal,M.,et al.

(2004).Polycomb group proteins Ring1A/B link ubiquitylation of his-tone H2A to heritable gene silencing and X inactivation.Dev.Cell7, 663–676.

Dejardin,J.,and Cavalli,G.(2004).Chromatin inheritance upon Zeste-mediated Brahma recruitment at a minimal cellular memory module.

EMBO J.23,857–868.

Dejardin,J.,Rappailles,A.,Cuvier,O.,Grimaud,C.,Decoville,M., Locker,D.,and Cavalli,G.(2005).Recruitment of Drosophila Poly-comb group proteins to chromatin by DSP1.Nature434,533–538.

Cell128,735–745,February23,2007a2007Elsevier Inc.743

Delaval,K.,and Feil,R.(2004).Epigenetic regulation of mammalian genomic imprinting.Curr.Opin.Genet.Dev.14,188–195.

Dellino,G.I.,Schwartz,Y.B.,Farkas,G.,McCabe,D.,Elgin,S.C.,and Pirrotta,V.(2004).Polycomb silencing blocks transcription initiation. Mol.Cell13,887–893.

Delsuc,F.,Brinkmann,H.,Chourrout,D.,and Philippe,H.(2006).Tu-nicates and not cephalochordates are the closest living relatives of vertebrates.Nature439,965–968.

Dou,Y.,Milne,T.A.,Tackett,A.J.,Smith,E.R.,Fukuda,A.,Wysocka, J.,Allis,C.D.,Chait,B.T.,Hess,J.L.,and Roeder,R.G.(2005).Physical association and coordinate function of the H3K4methyltransferase MLL1and the H4K16acetyltransferase MOF.Cell121,873–885.

Francis,N.J.,Kingston,R.E.,and Woodcock,C.L.(2004).Chromatin compaction by a polycomb group protein complex.Science306, 1574–1577.

Grimaud,C.,Bantignies,F.,Pal-Bhadra,M.,Ghana,P.,Bhadra,U., and Cavalli,G.(2006).RNAi Components Are Required for Nuclear Clustering of Polycomb Group Response Elements.Cell124,957–971.

Guitton,A.E.,and Berger,F.(2005).Control of reproduction by Poly-comb Group complexes in animals and plants.Int.J.Dev.Biol.49, 707–716.

Heard,E.(2005).Delving into the diversity of facultative heterochroma-tin:the epigenetics of the inactive X chromosome.Curr.Opin.Genet. Dev.15,482–489.

Hernandez-Munoz,I.,Lund,A.H.,van der Stoop,P.,Boutsma,E., Muijrers,I.,Verhoeven,E.,Nusinow,D.A.,Panning,B.,Marahrens, Y.,and van Lohuizen,M.(2005a).Stable X chromosome inactivation involves the PRC1Polycomb complex and requires histone MACROH2A1and the CULLIN3/SPOP ubiquitin E3ligase.Proc. https://www.sodocs.net/doc/034960848.html,A102,7635–7640.

Hernandez-Munoz,I.,Taghavi,P.,Kuijl,C.,Neefjes,J.,and van Lohui-zen,M.(2005b).Association of BMI1with polycomb bodies is dynamic and requires PRC2/EZH2and the maintenance DNA methyltransfer-ase DNMT1.Mol.Cell.Biol.25,11047–11058.

Hsieh,J.J.,Cheng,E.H.,and Korsmeyer,S.J.(2003).Taspase1:a thre-onine aspartase required for cleavage of MLL and proper HOX gene expression.Cell115,293–303.

Hughes,C.M.,Rozenblatt-Rosen,O.,Milne,T.A.,Copeland,T.D.,Lev-ine,S.S.,Lee,J.C.,Hayes,D.N.,Shanmugam,K.S.,Bhattacharjee,A., Biondi,C.A.,et al.(2004).Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8locus.Mol. Cell13,587–597.

Kagey,M.H.,Melhuish,T.A.,Powers,S.E.,and Wotton,D.(2005).Mul-tiple activities contribute to Pc2E3function.EMBO J.24,108–119.

Kahn,T.G.,Schwartz,Y.B.,Dellino,G.I.,and Pirrotta,V.(2006).Poly-comb complexes and the propagation of the methylation mark at the Drosophila Ubx gene.J.Biol.Chem.281,29064–29075.

Kim,D.H.,Villeneuve,L.M.,Morris,K.V.,and Rossi,J.J.(2006).Argo-naute-1directs siRNA-mediated transcriptional gene silencing in hu-man cells.Nat.Struct.Mol.Biol.13,793–797.

Kim,T.H.,Barrera,L.O.,Zheng,M.,Qu,C.,Singer,M.A.,Richmond, T.A.,Wu,Y.,Green,R.D.,and Ren,B.(2005).A high-resolution map of active promoters in the human genome.Nature436,876–880.

Klymenko,T.,Papp,B.,Fischle,W.,Kocher,T.,Schelder,M.,Fritsch, C.,Wild,B.,Wilm,M.,and Muller,J.(2006).A Polycomb group protein complex with sequence-speci?c DNA-binding and selective methyl-lysine-binding activities.Genes Dev.20,1110–1122.

Kurtzman,C.P.,and Robnett,C.J.(2003).Phylogenetic relationships among yeasts of the‘Saccharomyces complex’determined from multigene sequence analyses.FEMS Yeast Res.3,417–432.

Kuzmichev,A.,Jenuwein,T.,Tempst,P.,and Reinberg,D.(2004). Different EZH2-containing complexes target methylation of histone H1or nucleosomal histone H3.Mol.Cell14,183–193.Lee,T.I.,Jenner,R.G.,Boyer,L.A.,Guenther,M.G.,Levine,S.S., Kumar,R.M.,Chevalier,B.,Johnstone,S.E.,Cole,M.F.,Isono,K., et al.(2006).Control of developmental regulators by polycomb in human embryonic stem cells.Cell125,301–313.

Li,H.,Ilin,S.,Wang,W.,Duncan,E.M.,Wysocka,J.,Allis,C.D.,and Patel,D.J.(2006).Molecular basis for site-speci?c read-out of histone H3K4me3by the BPTF PHD?nger of NURF.Nature442,91–95.

Martin,C.,Cao,R.,and Zhang,Y.(2006).Substrate preferences of the EZH2histone methyltransferase complex.J.Biol.Chem.281,8365–8370.

Martinez,A.M.,and Cavalli,G.(2006).The role of polycomb group proteins in cell cycle regulation during development.Cell Cycle5, 1189–1197.

Milne,T.A.,Martin,M.E.,Brock,H.W.,Slany,R.K.,and Hess,J.L. (2005).Leukemogenic MLL fusion proteins bind across a broad region of the Hox a9locus,promoting transcription and multiple histone modi?cations.Cancer Res.65,11367–11374.

Mohd-Sarip,A.,Cleard,F.,Mishra,R.K.,Karch,F.,and Verrijzer,C.P. (2005).Synergistic recognition of an epigenetic DNA element by Plei-ohomeotic and a Polycomb core complex.Genes Dev.19,1755–1760.

Mohd-Sarip,A.,van der Knaap,J.A.,Wyman,C.,Kanaar,R.,Schedl, P.,and Verrijzer,C.P.(2006).Architecture of a Polycomb Nucleo-protein Complex.Mol.Cell24,91–100.

Mohd-Sarip,A.,Venturini,F.,Chalkley,G.E.,and Verrijzer,C.P.(2002). Pleiohomeotic can link polycomb to DNA and mediate transcriptional repression.Mol.Cell.Biol.22,7473–7483.

Muller,J.,and Kassis,J.A.(2006).Polycomb response elements and targeting of Polycomb group proteins in Drosophila.Curr.Opin.Genet. Dev.16,476–484.

Negre,N.,Hennetin,J.,Sun,L.V.,Lavrov,S.,Bellis,M.,White,K.P., and Cavalli,G.(2006).Chromosomal Distribution of PcG Proteins during Drosophila Development.PLoS Biol.4,e170.10.1371/journal. pbio.0040170.

Papp,B.,and Muller,J.(2006).Histone trimethylation and the mainte-nance of transcriptional ONand OFF states by trxG and PcG proteins. Genes Dev.20,2041–2054.

Petruk,S.,Sedkov,Y.,Riley,K.M.,Hodgson,J.,Schweisguth,F.,Hir-ose,S.,Jaynes,J.B.,Brock,H.W.,and Mazo,A.(2006).Transcription of bxd Noncoding RNAs Promoted by Trithorax Represses Ubx in cis by Transcriptional Interference.Cell127,1209–1221.

Pierce,R.J.,Wu,W.,Hirai,H.,Ivens,A.,Murphy,L.D.,Noel,C.,John-ston,D.A.,Artiguenave,F.,Adams,M.,Cornette,J.,et al.(2005).Evi-dence for a dispersed Hox gene cluster in the platyhelminth parasite Schistosoma mansoni.Mol.Biol.Evol.22,2491–2503.

Reynolds,P.A.,Sigaroudinia,M.,Zardo,G.,Wilson,M.B.,Benton, G.M.,Miller,C.J.,Hong,C.,Fridlyand,J.,Costello,J.F.,and Tlsty, T.D.(2006).Tumor suppressor P16INK4A regulates polycomb-mediated DNA hypermethylation in human mammary epithelial cells. J.Biol.Chem.281,24790–24802.

Sanchez-Elsner,T.,Gou,D.,Kremmer,E.,and Sauer,F.(2006).Non-coding RNAs of Trithorax Response Elements Recruit Drosophila Ash1 to Ultrabithorax.Science311,1118–1123.

Saurin,A.J.,Shao,Z.,Erdjument-Bromage,H.,Tempst,P.,and King-ston,R.E.(2001).A Drosophila Polycomb group complex includes Zeste and dTAFII proteins.Nature412,655–660.

Schlesinger,Y.,Straussman,R.,Keshet,I.,Farkash,S.,Hecht,M., Zimmerman,J.,Eden,E.,Yakhini,Z.,Ben-Shushan,E.,Reubinoff, B.E.,et al.(2006).Polycomb-mediated methylation on Lys27of histone H3pre-marks genes for de novo methylation in cancer.Nat. Genet.39,232–236.

Schmitt,S.,and Paro,R.(2006).RNA at the steering wheel.Genome Biol.7,218.

744Cell128,735–745,February23,2007a2007Elsevier Inc.

Schubert,D.,Primavesi,L.,Bishopp,A.,Roberts,G.,Doonan,J., Jenuwein,T.,and Goodrich,J.(2006).Silencing by plant Polycomb-group genes requires dispersed trimethylation of histone H3at lysine 27.EMBO J.25,4638–4649.

Schwartz,Y.B.,Kahn,T.G.,Nix,D.A.,Li,X.Y.,Bourgon,R.,Biggin,M., and Pirrotta,V.(2006).Genome-wide analysis of Polycomb targets in Drosophila melanogaster.Nat.Genet.38,700–705.

Schwartz,Y.B.,and Pirrotta,V.(2007).Polycomb silencing mecha-nisms and the management of genomic programmes.Nat.Rev.Genet. 8,9–22.

Seo,H.C.,Edvardsen,R.B.,Maeland,A.D.,Bjordal,M.,Jensen,M.F., Hansen,A.,Flaat,M.,Weissenbach,J.,Lehrach,H.,Wincker,P.,et al. (2004).Hox cluster disintegration with persistent anteroposterior order of expression in Oikopleura dioica.Nature431,67–71.

Shao,Z.,Raible, F.,Mollaaghababa,R.,Guyon,J.R.,Wu, C.T., Bender,W.,and Kingston,R.E.(1999).Stabilization of chromatin structure by PRC1,a Polycomb complex.Cell98,37–46.

Smith,S.T.,Petruk,S.,Sedkov,Y.,Cho,E.,Tillib,S.,Canaani,E.,and Mazo,A.(2004).Modulation of heat shock gene expression by the TAC1chromatin-modifying complex.Nat.Cell Biol.6,162–167. Spagnuolo,A.,Ristoratore,F.,Di Gregorio,A.,Aniello,F.,Branno,M., and Di Lauro,R.(2003).Unusual number and genomic organization of Hox genes in the tunicate Ciona intestinalis.Gene309,71–79. Sparmann,A.,and van Lohuizen,M.(2006).Polycomb silencers con-trol cell fate,development and cancer.Nat.Rev.Cancer6,846–856. Springer,N.M.,Danilevskaya,O.N.,Hermon,P.,Helentjaris,T.G.,Phil-lips,R.L.,Kaeppler,H.F.,and Kaeppler,S.M.(2002).Sequence relationships,conserved domains,and expression patterns for maize homologs of the polycomb group genes E(z),esc,and E(Pc).Plant Physiol.128,1332–1345.

Squazzo,S.L.,O’Geen,H.,Komashko,V.M.,Krig,S.R.,Jin,V.X.,Jang, S.,Margueron,R.,Reinberg,D.,Green,R.,and Farnham,P.J.(2006). Suz12binds to silenced regions of the genomein a cell-type-speci?c manner.Genome Res.16,890–900.

Sun,Z.W.,and Allis,C.D.(2002).Ubiquitination of histone H2B regu-lates H3methylation and gene silencing in yeast.Nature418,104–108. Sung,S.,He,Y.,Eshoo,T.W.,Tamada,Y.,Johnson,L.,Nakahigashi, K.,Goto,K.,Jacobsen,S.E.,and Amasino,R.M.(2006).Epigenetic maintenance of the vernalized state in Arabidopsis thaliana requires LIKE HETEROCHROMATIN PROTEIN1.Nat.Genet.38,706–710. Terranova,R.,Agherbi,H.,Boned,A.,Meresse,S.,and Djabali,M. (2006).Histone and DNA methylation defects at Hox genes in mice

expressing a SET domain-truncated form of Mll.Proc.Natl.Acad.

https://www.sodocs.net/doc/034960848.html,A103,6629–6634.

Tillib,S.,Petruk,S.,Sedkov,Y.,Kuzin,A.,Fujioka,M.,Goto,T.,and Mazo,A.(1999).Trithorax-and Polycomb-group response elements within an Ultrabithorax transcription maintenance unit consist of closely situated but separable sequences.Mol.Cell.Biol.19,5189–5202.

Tolhuis,B.,de Wit,E.,Muijrers,I.,Teunissen,H.,Talhout,W.,van Steensel,B.,and van Lohuizen,M.(2006).Genome-wide pro?ling of PRC1and PRC2Polycomb chromatin binding in Drosophila.Nat.

Genet.38,694–699.

van der Knaap,J.A.,Kumar,B.R.,Moshkin,Y.M.,Langenberg,K., Krijgsveld,J.,Heck,A.J.,Karch,F.,and Verrijzer,C.P.(2005).GMP synthetase stimulates histone H2B deubiquitylation by the epigenetic silencer USP7.Mol.Cell17,695–707.

Vire,E.,Brenner,C.,Deplus,R.,Blanchon,L.,Fraga,M.,Didelot,C., Morey,L.,Van Eynde,A.,Bernard,D.,Vanderwinden,J.M.,et al.

(2005).The Polycomb group protein EZH2directly controls DNA meth-ylation.Nature439,871–874.

Wang,H.,Wang,L.,Erdjument-Bromage,H.,Vidal,M.,Tempst,P., Jones,R.S.,and Zhang,Y.(2004a).Role of histone H2A ubiquitination in Polycomb silencing.Nature431,873–878.

Wang,L.,Brown,J.L.,Cao,R.,Zhang,Y.,Kassis,J.A.,and Jones,R.S.

(2004b).Hierarchical recruitment of polycomb group silencing com-plexes.Mol.Cell14,637–646.

Widschwendter,M.,Fiegl,H.,Egle,D.,Mueller-Holzner,E.,Spizzo,G., Marth,C.,Weisenberger,D.J.,Campan,M.,Young,J.,Jacobs,I.,and Laird,P.W.(2006).Epigenetic stem cell signature in cancer.Nat.

Genet.39,157–158.

Wysocka,J.,Myers,M.P.,Laherty,C.D.,Eisenman,R.N.,and Herr,W.

(2003).Human Sin3deacetylase and trithorax-related Set1/Ash2his-tone H3–K4methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1.Genes Dev.17,896–911.

Wysocka,J.,Swigut,T.,Milne,T.A.,Dou,Y.,Zhang,X.,Burlingame,

A.L.,Roeder,R.G.,Brivanlou,A.H.,and Allis,C.D.(2005).WDR5asso-

ciates with histone H3methylated at K4and is essential for H3K4 methylation and vertebrate development.Cell121,859–872.

Wysocka,J.,Swigut,T.,Xiao,H.,Milne,T.A.,Kwon,S.Y.,Landry,J., Kauer,M.,Tackett,A.J.,Chait,B.T.,Badenhorst,P.,et al.(2006).

A PHD?nger of NURF couples histone H3lysine4trimethylation

with chromatin remodelling.Nature442,86–90.

Cell128,735–745,February23,2007a2007Elsevier Inc.745

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概念模型实际上是现实世界到机器世界的一个中间层次。概念模型用于信息世界的建模,是现实世界到信息世界的第一层抽象,是数据库设计人员进行数据库设计的有力工具,也是数据库设计人员和用户之间进行交流的语言。 5、试述数据库系统三级模式结构 数据库系统的三级模式结构由外模式、模式和内模式组成。 特点:(1)数据结构化。(2)数据的共享性高,冗余度低,容易扩展。(3)数据独立性高。(4)数据有DBMS统一管理。 6、试述数据库系统的组成。 数据库系统一般由数据库、数据库管理系统(及其开发工具)、应用系统、数据库管理员和用户构成。 7、DBA 的职责是什么? 负责全面地管理和控制数据库系统。具体职责包括:①决定数据库的信息内容和结构;②决定数据库的存储结构和存取策略;③定义数据的安全性要求和完整性约束条件;④监督和控制数据库的使用和运行;⑤改进和重组数据库系统。 8、试述关系模型的三个组成部分。 答:关系模型由关系数据结构、关系操作集合和关系完整性约束三部分组成 9、试述关系数据语言的特点和分类。 答:关系数据语言可以分为三类: (1)关系代数语言。

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