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PDBsum entry 3ij0
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Gene regulation PDB id
3ij0

 

 

 

 

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Contents
Protein chain
359 a.a. *
Ligands
ALA-ARG-M3L-SER-
THR
Waters ×230
* Residue conservation analysis
PDB id:
3ij0
Name: Gene regulation
Title: Crystal structure of eed in complex with a trimethylated histone h3k9 peptide
Structure: Polycomb protein eed. Chain: a. Fragment: eed residues 77-441. Synonym: heed, wd protein associating with integrin cytoplasmic tails 1, wait-1. Engineered: yes. Mutation: yes. Histone h3k9 peptide. Chain: b.
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: eed. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Other_details: synthetic peptide
Resolution:
2.45Å     R-factor:   0.184     R-free:   0.244
Authors: N.Justin,M.L.Sharpe,S.Martin,W.R.Taylor,V.De Marco,S.J.Gamblin
Key ref: R.Margueron et al. (2009). Role of the polycomb protein EED in the propagation of repressive histone marks. Nature, 461, 762-767. PubMed id: 19767730
Date:
03-Aug-09     Release date:   15-Sep-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
O75530  (EED_HUMAN) -  Polycomb protein EED from Homo sapiens
Seq:
Struc: 		441 a.a.
359 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
Nature 461:762-767 (2009)
PubMed id: 19767730  
 
 
Role of the polycomb protein EED in the propagation of repressive histone marks.
R.Margueron, N.Justin, K.Ohno, M.L.Sharpe, J.Son, W.J.Drury, P.Voigt, S.R.Martin, W.R.Taylor, V.De Marco, V.Pirrotta, D.Reinberg, S.J.Gamblin.
 
  ABSTRACT  
 
Polycomb group proteins have an essential role in the epigenetic maintenance of repressive chromatin states. The gene-silencing activity of the Polycomb repressive complex 2 (PRC2) depends on its ability to trimethylate lysine 27 of histone H3 (H3K27) by the catalytic SET domain of the EZH2 subunit, and at least two other subunits of the complex: SUZ12 and EED. Here we show that the carboxy-terminal domain of EED specifically binds to histone tails carrying trimethyl-lysine residues associated with repressive chromatin marks, and that this leads to the allosteric activation of the methyltransferase activity of PRC2. Mutations in EED that prevent it from recognizing repressive trimethyl-lysine marks abolish the activation of PRC2 in vitro and, in Drosophila, reduce global methylation and disrupt development. These findings suggest a model for the propagation of the H3K27me3 mark that accounts for the maintenance of repressive chromatin domains and for the transmission of a histone modification from mother to daughter cells.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
23211769 C.A.Musselman, M.E.Lalonde, J.Côté, and T.G.Kutateladze (2012).
Perceiving the epigenetic landscape through histone readers.
  Nat Struct Mol Biol, 19, 1218-1227.  
23142980 C.A.Musselman, N.Avvakumov, R.Watanabe, C.G.Abraham, M.E.Lalonde, Z.Hong, C.Allen, S.Roy, J.K.Nuñez, J.Nickoloff, C.A.Kulesza, A.Yasui, J.Côté, and T.G.Kutateladze (2012).
Molecular basis for H3K36me3 recognition by the Tudor domain of PHF1.
  Nat Struct Mol Biol, 19, 1266-1272.
PDB code: 4hcz
22358331 C.Alabert, and A.Groth (2012).
Chromatin replication and epigenome maintenance.
  Nat Rev Mol Cell Biol, 13, 153-167.  
23104054 C.Ballaré, M.Lange, A.Lapinaite, G.M.Martin, L.Morey, G.Pascual, R.Liefke, B.Simon, Y.Shi, O.Gozani, T.Carlomagno, S.A.Benitah, and L.Di Croce (2012).
Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity.
  Nat Struct Mol Biol, 19, 1257-1265.
PDB code: 4bd3
22473383 E.L.Greer, and Y.Shi (2012).
Histone methylation: a dynamic mark in health, disease and inheritance.
  Nat Rev Genet, 13, 343-357.  
22290458 L.Daxinger, and E.Whitelaw (2012).
Understanding transgenerational epigenetic inheritance via the gametes in mammals.
  Nat Rev Genet, 13, 153-162.  
21336826 A.Grzenda, T.Ordog, and R.Urrutia (2011).
Polycomb and the emerging epigenetics of pancreatic cancer.
  J Gastrointest Cancer, 42, 100-111.  
  21141727 A.K.Upadhyay, and X.Cheng (2011).
Dynamics of histone lysine methylation: structures of methyl writers and erasers.
  Prog Drug Res, 67, 107-124.  
21174538 A.Piunti, and D.Pasini (2011).
Epigenetic factors in cancer development: polycomb group proteins.
  Future Oncol, 7, 57-75.  
22108599 B.Schuettengruber, A.M.Martinez, N.Iovino, and G.Cavalli (2011).
Trithorax group proteins: switching genes on and keeping them active.
  Nat Rev Mol Cell Biol, 12, 799-814.  
21321606 B.Zhu, and D.Reinberg (2011).
Epigenetic inheritance: Uncontested?
  Cell Res, 21, 435-441.  
21221116 C.Beisel, and R.Paro (2011).
Silencing chromatin: comparing modes and mechanisms.
  Nat Rev Genet, 12, 123-135.  
21243714 C.D.Allis, and T.W.Muir (2011).
Spreading chromatin into chemical biology.
  Chembiochem, 12, 264-279.  
21468892 C.Xu, and J.Min (2011).
Structure and function of WD40 domain proteins.
  Protein Cell, 2, 202-214.
PDB codes: 3e0c 3fm0 3i2n 3ow8
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Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation.
  Blood, 117, 2451-2459.  
21549310 F.W.Schmitges, A.B.Prusty, M.Faty, A.Stützer, G.M.Lingaraju, J.Aiwazian, R.Sack, D.Hess, L.Li, S.Zhou, R.D.Bunker, U.Wirth, T.Bouwmeester, A.Bauer, N.Ly-Hartig, K.Zhao, H.Chan, J.Gu, H.Gut, W.Fischle, J.Müller, and N.H.Thomä (2011).
Histone Methylation by PRC2 Is Inhibited by Active Chromatin Marks.
  Mol Cell, 42, 330-341.
PDB codes: 2yb8 2yba
21342762 G.Li, and D.Reinberg (2011).
Chromatin higher-order structures and gene regulation.
  Curr Opin Genet Dev, 21, 175-186.  
21660052 H.Cedar, and Y.Bergman (2011).
Epigenetics of haematopoietic cell development.
  Nat Rev Immunol, 11, 478-488.  
21423274 M.Yun, J.Wu, J.L.Workman, and B.Li (2011).
Readers of histone modifications.
  Cell Res, 21, 564-578.  
21362547 N.Avvakumov, A.Nourani, and J.Côté (2011).
Histone chaperones: modulators of chromatin marks.
  Mol Cell, 41, 502-514.  
21243712 P.Voigt, and D.Reinberg (2011).
Histone tails: ideal motifs for probing epigenetics through chemical biology approaches.
  Chembiochem, 12, 236-252.  
21414485 R.A.Young (2011).
Control of the embryonic stem cell state.
  Cell, 144, 940-954.  
21251103 R.Ishikawa, T.Ohnishi, Y.Kinoshita, M.Eiguchi, N.Kurata, and T.Kinoshita (2011).
Rice interspecies hybrids show precocious or delayed developmental transitions in the endosperm without change to the rate of syncytial nuclear division.
  Plant J, 65, 798-806.  
21248841 R.Margueron, and D.Reinberg (2011).
The Polycomb complex PRC2 and its mark in life.
  Nature, 469, 343-349.  
21522130 V.Hoppmann, T.Thorstensen, P.E.Kristiansen, S.V.Veiseth, M.A.Rahman, K.Finne, R.B.Aalen, and R.Aasland (2011).
The CW domain, a new histone recognition module in chromatin proteins.
  EMBO J, 30, 1939-1952.
PDB code: 2l7p
21116306 V.W.Zhou, A.Goren, and B.E.Bernstein (2011).
Charting histone modifications and the functional organization of mammalian genomes.
  Nat Rev Genet, 12, 7.  
21331095 X.Chen, J.Xiong, M.Xu, S.Chen, and B.Zhu (2011).
Symmetrical modification within a nucleosome is not required globally for histone lysine methylation.
  EMBO Rep, 12, 244-251.  
  20824077 A.Rechtsteiner, S.Ercan, T.Takasaki, T.M.Phippen, T.A.Egelhofer, W.Wang, H.Kimura, J.D.Lieb, and S.Strome (2010).
The histone H3K36 methyltransferase MES-4 acts epigenetically to transmit the memory of germline gene expression to progeny.
  PLoS Genet, 6, 0.  
20451393 C.U.Stirnimann, E.Petsalaki, R.B.Russell, and C.W.Müller (2010).
WD40 proteins propel cellular networks.
  Trends Biochem Sci, 35, 565-574.  
20974918 C.Xu, C.Bian, W.Yang, M.Galka, H.Ouyang, C.Chen, W.Qiu, H.Liu, A.E.Jones, F.MacKenzie, P.Pan, S.S.Li, H.Wang, and J.Min (2010).
Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2).
  Proc Natl Acad Sci U S A, 107, 19266-19271.
PDB codes: 3jpx 3jzg 3jzh 3jzn 3k26 3k27
20832727 D.Iliopoulos, M.Lindahl-Allen, C.Polytarchou, H.A.Hirsch, P.N.Tsichlis, and K.Struhl (2010).
Loss of miR-200 inhibition of Suz12 leads to polycomb-mediated repression required for the formation and maintenance of cancer stem cells.
  Mol Cell, 39, 761-772.  
20075857 D.Pasini, P.A.Cloos, J.Walfridsson, L.Olsson, J.P.Bukowski, J.V.Johansen, M.Bak, N.Tommerup, J.Rappsilber, and K.Helin (2010).
JARID2 regulates binding of the Polycomb repressive complex 2 to target genes in ES cells.
  Nature, 464, 306-310.  
20595228 E.I.Campos, and D.Reinberg (2010).
New chaps in the histone chaperone arena.
  Genes Dev, 24, 1334-1338.  
21170310 E.M.Mendenhall, R.P.Koche, T.Truong, V.W.Zhou, B.Issac, A.S.Chi, M.Ku, and B.E.Bernstein (2010).
GC-rich sequence elements recruit PRC2 in mammalian ES cells.
  PLoS Genet, 6, e1001244.  
21145479 E.Smith, and A.Shilatifard (2010).
The chromatin signaling pathway: diverse mechanisms of recruitment of histone-modifying enzymes and varied biological outcomes.
  Mol Cell, 40, 689-701.  
20123894 G.Li, R.Margueron, M.Ku, P.Chambon, B.E.Bernstein, and D.Reinberg (2010).
Jarid2 and PRC2, partners in regulating gene expression.
  Genes Dev, 24, 368-380.  
21060806 G.M.Lefevre, S.R.Patel, D.Kim, L.Tessarollo, and G.R.Dressler (2010).
Altering a histone H3K4 methylation pathway in glomerular podocytes promotes a chronic disease phenotype.
  PLoS Genet, 6, e1001142.  
20643336 G.Natoli (2010).
Maintaining cell identity through global control of genomic organization.
  Immunity, 33, 12-24.  
20646025 H.Furuhashi, and W.G.Kelly (2010).
The epigenetics of germ-line immortality: lessons from an elegant model system.
  Dev Growth Differ, 52, 527-532.  
20439426 H.M.Herz, and A.Shilatifard (2010).
The JARID2-PRC2 duality.
  Genes Dev, 24, 857-861.  
20658705 H.Richly, M.Lange, E.Simboeck, and L.Di Croce (2010).
Setting and resetting of epigenetic marks in malignant transformation and development.
  Bioessays, 32, 669-679.  
20871592 K.Kokura, L.Sun, M.T.Bedford, and J.Fang (2010).
Methyl-H3K9-binding protein MPP8 mediates E-cadherin gene silencing and promotes tumour cell motility and invasion.
  EMBO J, 29, 3673-3687.  
20923397 K.L.Yap, and M.M.Zhou (2010).
Keeping it in the family: diverse histone recognition by conserved structural folds.
  Crit Rev Biochem Mol Biol, 45, 488-505.  
20123906 M.Leeb, D.Pasini, M.Novatchkova, M.Jaritz, K.Helin, and A.Wutz (2010).
Polycomb complexes act redundantly to repress genomic repeats and genes.
  Genes Dev, 24, 265-276.  
20204433 M.N.Cruickshank, P.Besant, and D.Ulgiati (2010).
The impact of histone post-translational modifications on developmental gene regulation.
  Amino Acids, 39, 1087-1105.  
21203924 M.Xu, and B.Zhu (2010).
Nucleosome assembly and epigenetic inheritance.
  Protein Cell, 1, 820-829.  
20975044 N.S.Christophersen, and K.Helin (2010).
Epigenetic control of embryonic stem cell fate.
  J Exp Med, 207, 2287-2295.  
20671031 N.Van Dessel, L.Beke, J.Görnemann, N.Minnebo, M.Beullens, N.Tanuma, H.Shima, A.Van Eynde, and M.Bollen (2010).
The phosphatase interactor NIPP1 regulates the occupancy of the histone methyltransferase EZH2 at Polycomb targets.
  Nucleic Acids Res, 38, 7500-7512.  
  20112283 Q.Zhu, and A.A.Wani (2010).
Histone modifications: crucial elements for damage response and chromatin restoration.
  J Cell Physiol, 223, 283-288.  
21030644 R.Bonasio, S.Tu, and D.Reinberg (2010).
Molecular signals of epigenetic states.
  Science, 330, 612-616.  
20300089 R.Margueron, and D.Reinberg (2010).
Chromatin structure and the inheritance of epigenetic information.
  Nat Rev Genet, 11, 285-296.  
21123648 S.Kaneko, G.Li, J.Son, C.F.Xu, R.Margueron, T.A.Neubert, and D.Reinberg (2010).
Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA.
  Genes Dev, 24, 2615-2620.  
20685123 T.K.Barth, and A.Imhof (2010).
Fast signals and slow marks: the dynamics of histone modifications.
  Trends Biochem Sci, 35, 618-626.  
20008334 T.Suganuma, and J.L.Workman (2010).
WD40 repeats arrange histone tails for spreading of silencing.
  J Mol Cell Biol, 2, 81-83.  
20473313 U.Brykczynska, M.Hisano, S.Erkek, L.Ramos, E.J.Oakeley, T.C.Roloff, C.Beisel, D.Schübeler, M.B.Stadler, and A.H.Peters (2010).
Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa.
  Nat Struct Mol Biol, 17, 679-687.  
20658704 U.C.Lange, and R.Schneider (2010).
What an epigenome remembers.
  Bioessays, 32, 659-668.  
20485363 Y.Hirabayashi, and Y.Gotoh (2010).
Epigenetic control of neural precursor cell fate during development.
  Nat Rev Neurosci, 11, 377-388.  
20064463 G.A.Blobel, S.Kadauke, E.Wang, A.W.Lau, J.Zuber, M.M.Chou, and C.R.Vakoc (2009).
A reconfigured pattern of MLL occupancy within mitotic chromatin promotes rapid transcriptional reactivation following mitotic exit.
  Mol Cell, 36, 970-983.  
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The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.

 

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