Polycomb protein EED explained

Polycomb protein EED is a protein that in humans is encoded by the EED gene.^{[1] [2] [3]}

Function

Polycomb protein EED is a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein interacts with enhancer of zeste 2, the cytoplasmic tail of integrin β7, immunodeficiency virus type 1 (HIV-1) MA protein, and histone deacetylase proteins. This protein mediates repression of gene activity through histone deacetylation, and may act as a specific regulator of integrin function. Two transcript variants encoding distinct isoforms have been identified for this gene.

Clinical significance

In humans, a de-novo mutation in EED has been reported in an individual displaying symptoms similar to those of Weaver syndrome.^[4]

Interactions

EED has been shown to interact with:

• EZH2,^{[5] [6]}
• HDAC1,^[7]
• Histone deacetylase 2,^[7]
• ITGB7,
• PPP1R8,^[8] and
• TGS1.^[9]

Further reading

• Joseph AM, Kumar M, Mitra D . Nef: "necessary and enforcing factor" in HIV infection . Curr. HIV Res. . 3 . 1 . 87–94 . 2005 . 15638726 . 10.2174/1570162052773013 .
• Van Maele B, Debyser Z . HIV-1 integration: an interplay between HIV-1 integrase, cellular and viral proteins . AIDS Rev . 7 . 1 . 26–43 . 2005 . 15875659 .
• Jones CA, Ng J, Peterson AJ, Morgan K, Simon J, Jones RS . The Drosophila esc and E(z) proteins are direct partners in polycomb group-mediated repression . Mol. Cell. Biol. . 18 . 5 . 2825–34 . 1998 . 9566901 . 110661 . 10.1128/mcb.18.5.2825.
• van Lohuizen M, Tijms M, Voncken JW, Schumacher A, Magnuson T, Wientjens E . Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes . Mol. Cell. Biol. . 18 . 6 . 3572–9 . 1998 . 9584197 . 108938 . 10.1128/MCB.18.6.3572.
• Sewalt RG, van der Vlag J, Gunster MJ, Hamer KM, den Blaauwen JL, Satijn DP, Hendrix T, van Driel R, Otte AP . Characterization of interactions between the mammalian polycomb-group proteins Enx1/EZH2 and EED suggests the existence of different mammalian polycomb-group protein complexes . Mol. Cell. Biol. . 18 . 6 . 3586–95 . 1998 . 9584199 . 108940 . 10.1128/mcb.18.6.3586.
• Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K . Point mutations in the WD40 domain of Eed block its interaction with Ezh2 . Mol. Cell. Biol. . 18 . 10 . 5634–42 . 1998 . 9742080 . 109149 . 10.1128/MCB.18.10.5634.
• Peytavi R, Hong SS, Gay B, d'Angeac AD, Selig L, Bénichou S, Benarous R, Boulanger P . HEED, the product of the human homolog of the murine eed gene, binds to the matrix protein of HIV-1 . J. Biol. Chem. . 274 . 3 . 1635–45 . 1999 . 9880543 . 10.1074/jbc.274.3.1635 . free .
• van der Vlag J, Otte AP . Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation . Nat. Genet. . 23 . 4 . 474–8 . 1999 . 10581039 . 10.1038/70602 . 6748531 .
• Satijn DP, Hamer KM, den Blaauwen J, Otte AP . The polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in Xenopus embryos . Mol. Cell. Biol. . 21 . 4 . 1360–9 . 2001 . 11158321 . 99588 . 10.1128/MCB.21.4.1360-1369.2001 .
• Kuzmichev A, Nishioka K, Erdjument-Bromage H, Tempst P, Reinberg D . Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein . Genes Dev. . 16 . 22 . 2893–905 . 2002 . 12435631 . 187479 . 10.1101/gad.1035902 .
• Jin Q, van Eynde A, Beullens M, Roy N, Thiel G, Stalmans W, Bollen M . The protein phosphatase-1 (PP1) regulator, nuclear inhibitor of PP1 (NIPP1), interacts with the polycomb group protein, embryonic ectoderm development (EED), and functions as a transcriptional repressor . J. Biol. Chem. . 278 . 33 . 30677–85 . 2003 . 12788942 . 10.1074/jbc.M302273200 . free .
• Enünlü I, Pápai G, Cserpán I, Udvardy A, Jeang KT, Boros I . Different isoforms of PRIP-interacting protein with methyltransferase domain/trimethylguanosine synthase localizes to the cytoplasm and nucleus . Biochem. Biophys. Res. Commun. . 309 . 1 . 44–51 . 2003 . 12943661 . 10.1016/S0006-291X(03)01514-6 .
• Violot S, Hong SS, Rakotobe D, Petit C, Gay B, Moreau K, Billaud G, Priet S, Sire J, Schwartz O, Mouscadet JF, Boulanger P . The human polycomb group EED protein interacts with the integrase of human immunodeficiency virus type 1 . J. Virol. . 77 . 23 . 12507–22 . 2003 . 14610174 . 262565 . 10.1128/JVI.77.23.12507-12522.2003 .
• Witte V, Laffert B, Rosorius O, Lischka P, Blume K, Galler G, Stilper A, Willbold D, D'Aloja P, Sixt M, Kolanus J, Ott M, Kolanus W, Schuler G, Baur AS . HIV-1 Nef mimics an integrin receptor signal that recruits the polycomb group protein Eed to the plasma membrane . Mol. Cell . 13 . 2 . 179–90 . 2004 . 14759364 . 10.1016/S1097-2765(04)00004-8 . free .
• Cao R, Zhang Y . SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex . Mol. Cell . 15 . 1 . 57–67 . 2004 . 15225548 . 10.1016/j.molcel.2004.06.020 . free .
• Pasini D, Bracken AP, Jensen MR, Lazzerini Denchi E, Helin K . Suz12 is essential for mouse development and for EZH2 histone methyltransferase activity . EMBO J. . 23 . 20 . 4061–71 . 2004 . 15385962 . 524339 . 10.1038/sj.emboj.7600402 .

Notes and References

1. Rietzler M, Bittner M, Kolanus W, Schuster A, Holzmann B . The human WD repeat protein WAIT-1 specifically interacts with the cytoplasmic tails of beta7-integrins . J. Biol. Chem. . 273 . 42 . 27459–66 . Nov 1998 . 9765275 . 10.1074/jbc.273.42.27459 . free .
2. Schumacher A, Lichtarge O, Schwartz S, Magnuson T . The murine Polycomb-group gene eed and its human orthologue: functional implications of evolutionary conservation . Genomics . 54 . 1 . 79–88 . Jan 1999 . 9806832 . 10.1006/geno.1998.5509 .
3. Web site: Entrez Gene: EED embryonic ectoderm development.
4. Cohen AS, Tuysuz B, Shen Y, Bhalla SK, Jones SJ, Gibson WT . A novel mutation in EED associated with overgrowth . Journal of Human Genetics . 60 . 6 . 339–342 . Mar 2015 . 25787343 . 10.1038/jhg.2015.26 . 22055237 . free .
5. van Lohuizen M, Tijms M, Voncken JW, Schumacher A, Magnuson T, Wientjens E . Interaction of mouse polycomb-group (Pc-G) proteins Enx1 and Enx2 with Eed: indication for separate Pc-G complexes . Mol. Cell. Biol. . 18 . 6 . 3572–9 . Jun 1998 . 9584197 . 108938 . 10.1128/MCB.18.6.3572.
6. Denisenko O, Shnyreva M, Suzuki H, Bomsztyk K . Point mutations in the WD40 domain of Eed block its interaction with Ezh2 . Mol. Cell. Biol. . 18 . 10 . 5634–42 . Oct 1998 . 9742080 . 109149 . 10.1128/MCB.18.10.5634.
7. van der Vlag J, Otte AP . Transcriptional repression mediated by the human polycomb-group protein EED involves histone deacetylation . Nat. Genet. . 23 . 4 . 474–8 . Dec 1999 . 10581039 . 10.1038/70602 . 6748531 .
8. Jin Q, van Eynde A, Beullens M, Roy N, Thiel G, Stalmans W, Bollen M . The protein phosphatase-1 (PP1) regulator, nuclear inhibitor of PP1 (NIPP1), interacts with the polycomb group protein, embryonic ectoderm development (EED), and functions as a transcriptional repressor . J. Biol. Chem. . 278 . 33 . 30677–85 . Aug 2003 . 12788942 . 10.1074/jbc.M302273200 . free .
9. Enünlü I, Pápai G, Cserpán I, Udvardy A, Jeang KT, Boros I . Different isoforms of PRIP-interacting protein with methyltransferase domain/trimethylguanosine synthase localizes to the cytoplasm and nucleus . Biochem. Biophys. Res. Commun. . 309 . 1 . 44–51 . Sep 2003 . 12943661 . 10.1016/s0006-291x(03)01514-6.