10.1101/gad.1676208Access the most recent version at doi: 2008 22: 1265-1268
Genes Dev.
Tamaki Suganuma, Samantha G. Pattenden and Jerry L. Workman
Diver functions of WD40 repeat proteins in histone recognition
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Genes Dev. May 15, 2008 22: 1313-1318Ji-Joon Song, Joph D. Garlick and Robert E. Kingston Structural basis of histone H4 recognition by p55rvice
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PERSPECTIVE
Diver functions of WD40repeat proteins in histone recognition Tamaki Suganuma,Samantha G.Pattenden,and Jerry L.Workman1
Stowers Institute for Medical Rearch,Kansas City,Missouri64110,USA
WD40repeat proteins have been shown to bind the his-tone H3tail at the center of their-propeller structure. In contrast,in this issue of Genes&Development,Song and colleagues(pp.1313–1318)demonstrate that the WD40repeat protein p55binds a structured region of H4 through a novel binding pocket on the side of-propel-ler,illustrating a diversity of histone recognition by WD40repeat proteins.
The association of WD40repeat proteins with histones and nucleosomes is of increasing interest becau of their functions in a variety of histone/chromatin-modi-fying complexes.In this issue of Genes&Development, Song et al.(2008)solve the crystal structure of p55,a Drosophila ven-WD40-repeat protein.Binding of p55 is shown to be incompatible with the histone fold of H4 and results in a change in H4structure.The interaction of p55with H4is distinct from that of previously char-acterized WD40repeat proteins and utilizes a novel binding pocket on the side of the-propeller instead of the
center of the propeller.This novel p55–H4interac-tion extends the known contacts by which WD40repeat proteins recognize histones and reveals diversity in the manner in which this important recognition domain functions.
WD40repeat proteins are important for a variety of cellular functions
WD40repeats were first noted in the-subunit of the heterotrimeric GTP-binding protein(G protein)(Fong et al.1986).The G protein structure contained ven WD40 repeats.Each repeating unit formed one of ven-pro-peller blades with four small anti-parallel-sheets built into a toroidal structure with a tapered end and central canal(Wall et al.1995;Neer and Smith2000).The con-rved core of repeating units contained44–60residues that ended with tryptophan(W)and aspartate(D).Since the initial identification of the WD40repeats,>160WD40repeat proteins have been identified,with the ma-jority found in higher eukaryotes(Smith et al.1999). Each family member has between four and10copies of the WD40repeats.In general,WD40repeat proteins have been associated with a diver range of cellular pro-cess,including RNA processing,transcriptional regu-lation(Williams et al.1991;Hoey et al.1993),mitotic spindle formation(de Hostos et al.1991;Vaisman et al. 1995),regulation of vesicle formation and vesicular traf-ficking(Pryer et al.1993),and control of cell division (Feldman et al.1997).
Four WD40repeat proteins—WDR5,RbBP5,RbAp48/ 46(each with ven repeats)—and the Drosophila homo-log of RbAp48/46,p55,are components of histone-modi-fying complexes(Fig.1).WDR5is associated with SET domain-containing methyltransferas,such as Set1, MLL,MLL2,and MLL3/4(Wysocka et al.2005;Dou et al.2006;Mendjan et al.2006;Cho et al.2007).In addi-tion to its role in histone methylation,WDR5and WDS, the Drosophila homolog of WDR5,are associated with veral histone acetyltransfera(HAT)complexes, including the MSL(male-specific lethal)complex(Mend-jan et al.2006);the ATAC(Ada Two A-containing)com-plex,which functions as both an H3and H4HAT(Su-ganuma et al.2008);and MOF,a H4K16acetyltransfer-a complex(Dou et al.2005).Thus,WDR5plays important roles in multiple complexes that display dis-tinct catalytic activities on histone substrates.
RbAp48is another ven-WD40-repeat protein that was initially identified as a retinoblastoma protein(Rb)-binding protein(Qian et al.1993).RbAp48/46and its Drosophila homolog p55are associated with a variety of chromatin-regulating complexes that include chromatin asmbly factor CAF-1,(Tyler et al.1996;Verreault et al. 1996),Hat1(Parthun et al.1996;Verreault et al.1998), histone deacetyla HDAC1,the NuRD ATP-dependent chromatin remodeling complex(Hassig et al.1997;Xue et al.1998;Zhang et al.1998,1999;Kuzmichev et al. 2002),and the Extra Sex Combs(ES
C)and Enhancer of Zeste[E(Z)],ESC–E(Z)complex,which is a type of Poly-comb group(PcG)histone methyltransfera(HMT) complex(Czermin et al.2002;Muller et al.2002).The p55protein has been shown to associate with newly syn-thesized H4(Verreault et al.1996),and the RbAp48/46 family to which it belongs is thought to play an impor-tant role in histone metabolism.
[Keywords:p55;Nurf55;RbAp48;histone;chromatin;WD40]
1Corresponding author.
E-MAIL jlw@stowers-institute;FAX(816)926-4692.
Article is online sdev/cgi/doi/10.1101/gad.1676208.
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WD40repeat protein structure
WD40repeat proteins play a vital role in a variety of chromatin-modifying complexes.The structure of WDR5,a ven-WD40-repeat protein that is a compo-nent of the SET1HMT complex family,has bee
n well characterized.Initial peptide-binding studies with WDR5showed that it bound preferentially to dimethyl-ated Lys 4on histone H3(H3K4me2)but was also re-quired for K4trimethylation (Fig.1;Wysocka et al.2005).Several crystal structures of WDR5associated with peptides reprenting various states of H3K4meth-ylation have clarified this issue (Couture et al.2006;Han et al.2006;Ruthenburg et al.2006;Schuetz et al.2006).While the exact type of bonding between H3and WDR5remains controversial,it is generally accepted that H3R2,located on the expod tail of histone H3,con-tacts the center of the WDR5-propeller structure (Fig.1;Couture et al.2006;Han et al.2006;Ruthenburg et al.2006;Schuetz et al.2006).Indeed,recent studies re-vealed that methylation of H3R2by the PRMT6meth-yltransfera impedes both H3K4trimethylation and re-cruitment of WDR5(Guccione et al.2007;Hyllus et al.2007).R2is also important for the recognition of meth-ylated K4by CHD1(Flanagan et al.2005).Analysis of WDR5crystals have shown that while this protein can interact with all forms of methylated K4,it has addi-tional contacts with H3K4me2via a pair of conventional and unconventional hydrogen bonds.Thus,it would ap-pear that WDR5binds to H3K4me2and prents it to a SET1family methyltransfera for subquent trimeth-ylation (Ruthenburg et al.2006;Schuetz et al.2006).In-deed,one biochemical study demonstrated that WDR5mediated an interaction between the catalytic subunit of the MLL HMT complex and the histone substrate (Dou et al.2006).
In contrast to the H3tail binding the center of the WD40repeat -propeller in WDR5,Song et al.(2008)have discovered a very different interaction of a WD40repeat protein with histone H4that includes contacts with normally folded portions of the histone.The p55protein was initially identified as a subunit of the Dro-sophila CAF-1(dCAF1).Its human homolog,RbAp48/46,has been shown to bind H4in vitro (Verreault et al.1998).The current structural study shows p55binding to the first helix (helix1-H4,31–41amino acids)of an H4peptide (15–41amino acids)via a binding pocket formed by its N-terminal ␣-helix (␣1)and a binding loop protrud-ing from the venth blade of the -propeller structure (Fig.1).Thus,unlike WDR5,which binds the central canal of the WD40repeat -propeller,p55interacts with H4via a novel pocket on the side of the propeller of the structure.The p55/RbAp48␣1helix contains a unique quence that is not prent in either WDR5or its Dro-sophila homolog,WDS,which contributes to this bind-ing site (Fig.1).This binding pocket is not altered by interaction with H4,but the histone fold domain of H4must be distorted in order to bind p55.Thus,the inter-action of p55with a structured domain of H4is quite distinct from the interaction of WDR5with the protrud-ing H3tail.
While the structure prented demonstrates the mode of p55binding to histone H4,p55also appears to bind to histone H3.Surface plasmon resonance (SPR)experi-ments demonstrate that an H4R39A
mutation disrupts p55binding to histone H4alone (Song et al.2008).How-ever,in the context of an H32–H4R39A 2mutant histone tetramer,p55can still bind.In addition,the p55D362A and D365A mutants,which were mutated in the H4-binding loop of p55,were still able to bind H3,although to a lesr degree than the wild-type protein.Song et al.(2008)suggest that p55binds different surfaces on H3and H4and that the interaction with H4influences bind-ing of p55to H3.Through the interactions,p55may rve to prent the H3tail for modification by various p55-containing complexes.
Interaction of the p55-binding pocket with H4appears to be context-dependent.Within the Hat1HAT com-plex,Song et al.(2008)showed that the interaction of p55with H4-␣1is important for H4acetylation.By contrast,mutations in the H4-binding pocket disrupted the ability of p55to asmble into the PRC2(Polycomb Repressor Complex 2)H3K27methyltransfera complex.The data suggest that in the context of the PRC2complex the p55-binding pocket may interact with other PRC2sub-units and not with H4.Thus,the p55WD40repeat do-main appears to be multifunctional.
新年窗花The idea that WD40repeat proteins can rve as adap-tors or prentation molecules (Ruthenburg et al.2007)is an area of interest.Remarkably,the human ISWI-con-taining ATP-dependent chromatin remodeling complex NURF (nucleosome remodeling factor)contains both WDR5and RbAp48(the hu
man p55homolog).This complex also contains BPTF (bromodomain and PHD finger transcription factor),which has a PHD finger do-main that was shown to mediate a direct
preferential
Figure 1.Schematic domain structure of ven-WD40-repeat-containing proteins.(Black triangles)Generally accepted histoneH3recognition sites;(red triangles)structurally rearranged phenylalanine by binding his-tone H3;(␣1and ␣2)␣-helix1and ␣-helix2;(black filled circles)backbone of t
he binding loop;(Z)putative leu-cine zipper domain;(Q)glutamine-rich domain;(GP)glycine/proline-rich domain;(CcN)containing nuclear localization and phosphorylation sites;(Ser/Pro-rich)rine/threonine/proline-rich domain.
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association with the H3K4me3histone tail (Wysocka et al.2006).siRNA knockdown of WDR5leads to reduction of H3K4me3and a partial disruption of the association of BPTF with chromatin (Wysocka et al.2006).Thus,fac-tors other that WDR5alone may contribute to the asso-ciation of NURF with chromatin.The possibility that one of the factors is RbAp48/p55would be interesting to address.
WD40repeat protein interactions with histones are not limited to the WD40repeat domains;other,less con-rved domains can play an important role.In some cas,it is not the WD40repeat domain that is involved in histone recognition.The Drosophila WD40repeat protein Groucho and its mammalian h
omolog TLE1(Transducin-like Enhancer of split 1)are transcriptional corepressors involved in various signaling pathways.The proteins interact with H3and H4through an N-terminal conrved glutamine-rich (Q)domain and a gly-cine/proline-rich (GP)domain (Fig.1).The ven-repeat WD40domain mediates interactions with DNA-binding transcription factors such as Engrailed and Dorsal (Pick-les et al.2002).Pickles et al.(2002)compared the phe-notypes resulting from misn mutation of three dif-ferent positions of the WD40repeat domain within the Caenorhabditis elegans Groucho/TLE homolog UNC-37(Fig.1).A mutation that perturbed the WD40-propeller structure disrupted UNC-37binding to the UNC4ho-meodomain transcription factor (Pickles et al.2002).UNC-37contains additional GP and Q domains that are required for interaction with H3and HDACs (Chen et al.1999).Thus,the binding of transcription factors by the WD40repeat domain might facilitate or target HDAC activity.An analogous function of WD40repeats is found in the yeast Tup1protein.Tup1is a global tran-scriptional repressor with a structure similar to Groucho/TLE (Sprague et al.2000).Tup1directly inter-acts with the N termini of H3and H4through its repres-sion domain,which is on the N-terminal side of the WD40repeats (Edmondson et al.1996).In Tup1,how-ever,the WD40repeats are required for promoter target-ing through association with DNA-binding proteins such as ␣2(Fig.1;Edmondson et al.1996).Conclusion
Whether it is WDR5prentation of H3K4me for sub-quent methylation,p55modification of H4structure,or interaction with transcription factors by Groucho/TLE1/Tup1,WD40repeat proteins play important roles in chromatin function and gene regulation.A priori,one might have expected proteins with related domains to follow some paradigm for chromatin interactions.WD40repeat proteins,however,are revealing a great deal of functional diversity in how they establish their interac-tions with histones and chromatin.References
Chen,G.,Fernandez,J.,Mische,S.,and Courey,A.J.1999.A
functional interaction between the histone deacetyla Rpd3and the corepressor groucho in Drosophila development.Genes &Dev.13:2218–2230.
Cho,Y.W.,Hong,T.,Hong,S.,Guo,H.,Yu,H.,Kim,D.,Guszc-zynski,T.,Dressler,G.R.,Copeland,T.D.,Kalkum,M.,et al.2007.PTIP associates with MLL3-and MLL4-containing his-tone H3lysine 4methyltransfera complex.J.Biol.Chem.282:20395–20406.
Couture,J.F.,Collazo,E.,and Trievel,R.C.2006.Molecular recognition of histone H3by the WD40protein WDR5.Nat.Struct.Mol.Biol.13:698–703.
Czermin,B.,Melfi,R.,McCabe,D.,Seitz,V.,Imhof,A.,and Pirrotta,V.2002.Drosophila enhancer of Zeste/ESC com-plexes have a histone H3methyltransfera activity that marks chromosomal Polycomb sites.Cell 111:185–196.de Hostos,E.L.,Bradtke,B.,Lottspeich,F.,Guggenheim,R.,and Gerisch,G.1991.Coronin,an actin binding protein of Dic-tyostelium discoideum localized to cell surface projections,has quence similarities to G protein subunits.EMBO J.10:4097–4104.
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 H3K4methyltransfera MLL1and the H4K16acetyl-transfera MOF.Cell 121:873–885.
矫情镇物
Dou,Y.,Milne,T.A.,Ruthenburg,A.J.,Lee,S.,Lee,J.W.,Ver-dine,G.L.,Allis,C.D.,and Roeder,R.G.2006.Regulation of MLL1H3K4methyltransfera activity by its core compo-nents.Nat.Struct.Mol.Biol.13:713–719.
Edmondson,D.G.,Smith,M.M.,and Roth,S.Y.1996.Repres-sion domain of the yeast global repressor Tup1interacts di-rectly with histones H3and H4.Genes &Dev.10:1247–1259.
Feldman,R.M.,Correll,C.C.,Kaplan,K.B.,and Deshaies,R.J.1997.A complex of Cdc4p,Skp1p,and Cdc53p/cullin cata-lyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p.Cell 91:221–230.
批改作业评语
Flanagan,J.F.,Mi,L.Z.,Chruszcz,M.,Cymborowski,M.,Clines,K.L.,Kim,Y.,Minor,W.,Rastinejad,F.,and Kho-rasanizadeh,S.2005.Double chromodomains cooperate to recognize the methylated histone H3tail.Nature 438:1181–1185.
Fong,H.K.,Hurley,J.B.,Hopkins,R.S.,Miake-Lye,R.,Johnson,M.S.,Doolittle,R.F.,and Simon,M.I.1986.Repetitive g-mental structure of the transducin subunit:Homology with the CDC4gene and identification of related mRNAs.Proc.Natl.Acad.Sci.83:2162–2166.
Guccione,E.,Bassi,C.,Casadio,F.,Martinato,F.,Cesaroni,M.,Schuchlautz,H.,Luscher,B.,and Amati,B.2007.Methyla-tion of histone H3R2by PRMT6and H3K4by an MLL com-plex are mutually exclusive.Nature 449:933–937.
Han,Z.,Guo,L.,Wang,H.,Shen,Y.,Deng,X.W.,and Chai,J.2006.Structural basis for the specific recognition of meth-ylated histone H3lysine 4by the WD-40protein WDR5.Mol.Cell 22:137–144.
Hassig,C.A.,Fleischer,T.C.,Billin,A.N.,Schreiber,S.L.,and Ayer,D.E.1997.Histone deacetyla activity is required for full transcriptional repression by mSin3A.Cell 89:341–347.Hoey,T.,Weinzierl,R.O.,Gill,G.,Chen,J.L.,Dynlacht,B.D.,and Tjian,R.1993.Molecular cloning and functional analy-sis of Drosophila TAF110reveal properties expected of co-activators.Cell 72:247–26
0.
Hyllus,D.,Stein,C.,Schnabel,K.,Schiltz,E.,Imhof,A.,Dou,Y.,Hsieh,J.,and Bauer,U.M.2007.PRMT6-mediated meth-ylation of R2in histone H3antagonizes H3K4trimethyl-ation.Genes &Dev.21:3369–3380.
Kuzmichev,A.,Nishioka,K.,Erdjument-Bromage,H.,Tempst,
Diver functions of WD40repeats
GENES &DEVELOPMENT 1267
Cold Spring Harbor Laboratory Press on May 14, 2013 - Published by genesdev.cshlp Downloaded from
P.,and Reinberg,D.2002.Histone methyltransfera activ-ity associated with a human multiprotein complex contain-ing the Enhancer of Zeste protein.Genes&Dev.16:2893–2905.
Mendjan,S.,Taipale,M.,Kind,J.,Holz,H.,Gebhardt,P., Schelder,M.,Vermeulen,M.,Buscaino, A.,Duncan,K., Mueller,J.,et al.2006.Nuclear pore components are in-volved in the transcriptional regulation of dosage compen-sation in Drosophila.Mol.Cell21:811–823.
Muller,J.,Hart,C.M.,Francis,N.J.,Vargas,M.L.,Sengupta,A., Wild,B.,Miller,E.L.,O’Connor,M.B.,Kingston,R.E.,and Simon,J.A.2002.Histone methyltransfera activity of a Drosophila Polycomb group repressor complex.Cell111: 197–208.
Neer,E.J.and Smith,T.F.2000.A groovy new structure.Proc.
Natl.Acad.Sci.97:960–962.
Parthun,M.R.,Widom,J.,and Gottschling,D.E.1996.The ma-jor cytoplasmic histone acetyltransfera in yeast:Links to chromatin replication and histone metabolism.Cell87:85–
环境执法94.
Pickles,L.M.,Roe,S.M.,Hemingway,E.J.,Stifani,S.,and Pearl, L.H.2002.Crystal structure of the C-terminal WD40repeat domain of the human Groucho/TLE1transcriptional core-pressor.Structure10:751–761.
Pryer,N.K.,Salama,N.R.,Schekman,R.,and Kair,C.A.1993.
Cytosolic Sec13p complex is required for vesicle formation from the endoplasmic reticulum in vitro.J.Cell Biol.120: 865–875.
Qian,Y.W.,Wang,Y.C.,Hollingsworth Jr.,R.E.,Jones,D.,Ling, N.,and Lee,E.Y.1993.A retinoblastoma-binding protein related to a negative regulator of Ras in yeast.Nature364: 648–652.
Ruthenburg,A.J.,Wang,W.,Graybosch,D.M.,Li,H.,Allis,
C.D.,Patel,D.J.,and Verdine,G.L.2006.Histone H3recog-
nition and prentation by the WDR5module of the MLL1 complex.Nat.Struct.Mol.Biol.13:704–712. Ruthenburg,A.J.,Allis,C.D.,and Wysocka,J.2007.Methyla-tion of lysine4on histone H3:Intricacy of writing and read-ing a single epigenetic mark.Mol.Cell25:15–30. Schuetz,A.,Allali-Hassani,A.,Martin,F.,Loppnau,P.,Vedadi, M.,Bochkarev,A.,Plotnikov,A.N.,Arrowsmith,C.H.,and Min,J.2006.Structural basis for molecular recognition and prentation of histone H3by WDR5.EMBO J.25:4245–4252.
Smith,T.F.,Gaitatzes,C.,Saxena,K.,and Neer,E.J.1999.The WD repeat:A common architecture for diver functions.
Trends Biochem.Sci.24:181–185.
Song,J.-J.,Garlick,J.D.,and Kingston,R.E.2008.Structural basis of histone H4recognition by p55.Gen
es&Dev.(this issue)doi:10.1101/gad.1653308.早恋的好处
Sprague,E.R.,Redd,M.J.,Johnson,A.D.,and Wolberger,C.
2000.Structure of the C-terminal domain of Tup1,a core-pressor of transcription in yeast.EMBO J.19:3016–3027. Suganuma,T.,Gutierrez,J.L.,Li,B.,Florens,L.,Swanson,S.K., Washburn,M.P.,Abmayr,S.M.,and Workman,J.L.2008.
ATAC is a double histone acetyltransfera complex that stimulates nucleosome sliding.Nat.Struct.Mol.Biol.15: 364–367
文化与社会Tyler,J.K.,Bulger,M.,Kamakaka,R.T.,Kobayashi,R.,and Ka-donaga,J.T.1996.The p55subunit of Drosophila chromatin asmbly factor1is homologous to a histone deacetyla-associated protein.Mol.Cell.Biol.16:6149–6159. Vaisman,N.,Tsouladze,A.,Robzyk,K.,Ben-Yehuda,S.,Ku-piec,M.,and Kassir,Y.1995.The role of Saccharomyces cerevisiae Cdc40p in DNA replication and mitotic spindle for-mation and/or maintenance.Mol.Gen.Genet.247:123–136.Verreault,A.,Kaufman,P.D.,Kobayashi,R.,and Stillman,B.
1996.Nucleosome asmbly by a complex of CAF-1and acetylated histones H3/H4.Cell87:95–104.
Verreault,A.,Kaufman,P.D.,Kobayashi,R.,and Stillman,B.
1998.Nucleosomal DNA regulates the core-histone-binding subunit of the human Hat1acetyltransfera.Curr.Biol.8: 96–108.
Wall,M.A.,Coleman,D.E.,Lee,E.,Iniguez-Lluhi,J.A.,Posner,
B.A.,Gilman,A.G.,and Sprang,S.R.1995.The structure of
the G protein heterotrimer Gi␣11␥2.Cell83:1047–1058.
Williams,F.E.,Varanasi,U.,and Trumbly,R.J.1991.The CYC8 and TUP1proteins involved in gluco repression in Saccha-romyces cerevisiae are associated in a protein complex.Mol.
Cell.Biol.11:3307–3316.
Wysocka,J.,Swigut,T.,Milne,T.A.,Dou,Y.,Zhang,X.,Bur-lingame,A.L.,Roeder,R.G.,Brivanlou,A.H.,and Allis,C.D.
2005.WDR5associates with histone H3methylated at K4 and is esntial for H3K4methylation and vertebrate devel-opment.Cell121:859–872.
Wysocka,J.,Swigut,T.,Xiao,H.,Milne,T.A.,Kwon,S.Y.,Lan-dry,J.,Kauer,M.,Tackett,A.J.,Chait,B.T.,Badenhorst,P., et al.2006.A PHD finger of NURF couples histone H3lysine 4trimethylation with chromatin remodelling.Nature442: 86–90.
Xue,Y.,Wong,J.,Moreno,G.T.,Young,M.K.,Cote,J.,and Wang,W.1998.NURD,a novel complex with both ATP-dependent chromatin-remodeling and histone deacetyla activities.Mol.Cell2:851–861.
Zhang,Y.,LeRoy,G.,Seelig,H.P.,Lane,W.S.,and Reinberg,D.
1998.The dermatomyositis-specific autoantigen Mi2is a component of a complex containing histone deacetyla and nucleosome remodeling activities.Cell95:279–289. Zhang,Y.,Ng,H.H.,Erdjument-Bromage,H.,Tempst,P.,Bird,
A.,and Reinberg,D.1999.Analysis of the NuRD subunits
reveals a histone deacetyla core complex and a connection with DNA methylation.Genes&Dev.13:1924–1935.
Suganuma et al.
1268GENES&DEVELOPMENT
Cold Spring Harbor Laboratory Press on May 14, 2013 - Published by
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