title: Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination.
abstract: Nuclear receptors activate transcription by recruiting multiple coactivators to the promoters of specific target genes. The functional synergy of the p160 coactivators [steroid receptor coactivator-1, glucocorticoid receptor interacting protein (GRIP1), or the activator for thyroid hormone and retinoid receptors], the histone acetyltransferases cAMP response element binding protein binding protein (CBP) and p300 and the histone methyltransferase coactivator-associated arginine methyltransferase (CARM1) depends on the methyltransferase activity of CARM1. CARM1 methylates histone H3 and other factors including the N-terminal region of p300. Here, we report that CARM1 also methylates Arg-2142 within the C-terminal GRIP1 binding domain (GBD) of p300. In the GBD, both Arg-2088 and Arg-2142 are important for binding GRIP1. Methylation of Arg-2142 inhibits the bimolecular interaction of GRIP1 to p300 in vitro and in vivo. This methylation mark of p300 GBD is removed by peptidyl deiminase 4, thereby enhancing the p300-GRIP1 interaction. These methylation and demethylimination events also alter the conformation and activity of the coactivator complex and regulate estrogen receptor-mediated transcription, and they thus represent unique mechanisms for regulating coactivator complex assembly, conformation, and function.
authors.affiliation: Department of Pathology, University of Southern California, 2011 Zonal Avenue, HMR 301, Los Angeles, CA 90089, USA.
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Scott A
authors.initials: SA
authors.lastname: Coonrod
authors.forename: W Lee
authors.initials: WL
authors.lastname: Kraus
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Jelinek
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stallcup
mesh_terms: D001120:Arginine / Q000378:metabolism*; D001665:Binding Sites; D006801:Humans; D008745:Methylation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000502:physiology; D051958:Nuclear Receptor Coactivator 2; D011487:Protein Conformation; D011484:Protein-Arginine N-Methyltransferases / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology; D015534:Trans-Activators / Q000737:chemistry* / Q000502:physiology; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: C498001:NCOA2 protein, human; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D001120:Arginine; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1
references.citation: Mol Cell Biol. 1999 Dec;19(12):8123-35
references.pmid: 10567538
references.citation: Science. 1999 Jun 25;284(5423):2174-7
references.pmid: 10381882
references.citation: Genes Dev. 2000 Jan 15;14(2):121-41
references.pmid: 10652267
references.citation: Science. 2000 Feb 18;287(5456):1262-5
references.pmid: 10678832
references.citation: Mol Cell Biol. 2000 Mar;20(6):2031-42
references.pmid: 10688650
references.citation: J Biol Chem. 2000 Dec 29;275(52):40810-6
references.pmid: 11010967
references.citation: Cell. 2000 Dec 8;103(6):843-52
references.pmid: 11136970
references.citation: J Biol Chem. 2001 Apr 27;276(17):13505-8
references.pmid: 11279224
references.citation: Curr Opin Cell Biol. 2001 Jun;13(3):263-73
references.pmid: 11343896
references.citation: Genes Dev. 2001 Sep 15;15(18):2343-60
references.pmid: 11562345
references.citation: Mol Cell. 2001 Sep;8(3):581-90
references.pmid: 11583620
references.citation: EMBO J. 2001 Nov 1;20(21):6084-94
references.pmid: 11689448
references.citation: Curr Biol. 2001 Dec 11;11(24):1981-5
references.pmid: 11747826
references.citation: Science. 2001 Dec 21;294(5551):2507-11
references.pmid: 11701890
references.citation: Nature. 2002 Jan 31;415(6871):549-53
references.pmid: 11823864
references.citation: Trends Endocrinol Metab. 2002 Mar;13(2):55-60
references.pmid: 11854019
references.citation: J Biol Chem. 2002 Mar 15;277(11):9054-61
references.pmid: 11782467
references.citation: Cell. 2002 Feb 22;108(4):465-74
references.pmid: 11909518
references.citation: Mol Cell Biol. 2002 Jun;22(11):3621-32
references.pmid: 11997499
references.citation: Science. 2002 Jun 21;296(5576):2232-5
references.pmid: 12077419
references.citation: Cell. 2002 Jun 28;109(7):801-6
references.pmid: 12110177
references.citation: EMBO J. 2002 Oct 15;21(20):5457-66
references.pmid: 12374746
references.citation: EMBO Rep. 2002 Dec;3(12):1188-94
references.pmid: 12446572
references.citation: Mol Cell. 2003 Mar;11(3):695-707
references.pmid: 12667452
references.citation: Cell. 2003 Dec 12;115(6):751-63
references.pmid: 14675539
references.citation: Cell. 2004 Jun 11;117(6):735-48
references.pmid: 15186775
references.citation: Cell. 2004 Sep 3;118(5):545-53
references.pmid: 15339660
references.citation: Science. 2004 Oct 8;306(5694):279-83
references.pmid: 15345777
references.citation: Annu Rev Biochem. 1994;63:451-86
references.pmid: 7979245
references.citation: Cell. 1995 Dec 15;83(6):841-50
references.pmid: 8521508
references.citation: Mol Cell. 1999 Nov;4(5):725-34
references.pmid: 10619020
references.citation: Cell. 1996 May 3;85(3):403-14
references.pmid: 8616895
references.citation: Cell. 1997 Aug 8;90(3):569-80
references.pmid: 9267036
references.citation: Cell. 1999 Sep 3;98(5):675-86
references.pmid: 10490106