5isi

Structural highlights

Function

[CARM1_MOUSE] Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activates transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]}

References

1. ↑ Chen D, Ma H, Hong H, Koh SS, Huang SM, Schurter BT, Aswad DW, Stallcup MR. Regulation of transcription by a protein methyltransferase. Science. 1999 Jun 25;284(5423):2174-7. PMID:10381882
2. ↑ Schurter BT, Koh SS, Chen D, Bunick GJ, Harp JM, Hanson BL, Henschen-Edman A, Mackay DR, Stallcup MR, Aswad DW. Methylation of histone H3 by coactivator-associated arginine methyltransferase 1. Biochemistry. 2001 May 15;40(19):5747-56. PMID:11341840
3. ↑ Xu W, Chen H, Du K, Asahara H, Tini M, Emerson BM, Montminy M, Evans RM. A transcriptional switch mediated by cofactor methylation. Science. 2001 Dec 21;294(5551):2507-11. Epub 2001 Nov 8. PMID:11701890 doi:10.1126/science.1065961
4. ↑ Chen SL, Loffler KA, Chen D, Stallcup MR, Muscat GE. The coactivator-associated arginine methyltransferase is necessary for muscle differentiation: CARM1 coactivates myocyte enhancer factor-2. J Biol Chem. 2002 Feb 8;277(6):4324-33. Epub 2001 Nov 16. PMID:11713257 doi:http://dx.doi.org/10.1074/jbc.M109835200
5. ↑ Koh SS, Li H, Lee YH, Widelitz RB, Chuong CM, Stallcup MR. Synergistic coactivator function by coactivator-associated arginine methyltransferase (CARM) 1 and beta-catenin with two different classes of DNA-binding transcriptional activators. J Biol Chem. 2002 Jul 19;277(29):26031-5. Epub 2002 Apr 30. PMID:11983685 doi:http://dx.doi.org/10.1074/jbc.M110865200
6. ↑ Lee YH, Koh SS, Zhang X, Cheng X, Stallcup MR. Synergy among nuclear receptor coactivators: selective requirement for protein methyltransferase and acetyltransferase activities. Mol Cell Biol. 2002 Jun;22(11):3621-32. PMID:11997499
7. ↑ Yadav N, Lee J, Kim J, Shen J, Hu MC, Aldaz CM, Bedford MT. Specific protein methylation defects and gene expression perturbations in coactivator-associated arginine methyltransferase 1-deficient mice. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6464-8. Epub 2003 May 19. PMID:12756295 doi:http://dx.doi.org/10.1073/pnas.1232272100
8. ↑ Lee YH, Campbell HD, Stallcup MR. Developmentally essential protein flightless I is a nuclear receptor coactivator with actin binding activity. Mol Cell Biol. 2004 Mar;24(5):2103-17. PMID:14966289
9. ↑ An W, Kim J, Roeder RG. Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53. Cell. 2004 Jun 11;117(6):735-48. PMID:15186775 doi:10.1016/j.cell.2004.05.009
10. ↑ Covic M, Hassa PO, Saccani S, Buerki C, Meier NI, Lombardi C, Imhof R, Bedford MT, Natoli G, Hottiger MO. Arginine methyltransferase CARM1 is a promoter-specific regulator of NF-kappaB-dependent gene expression. EMBO J. 2005 Jan 12;24(1):85-96. Epub 2004 Dec 16. PMID:15616592 doi:http://dx.doi.org/10.1038/sj.emboj.7600500
11. ↑ Teyssier C, Ou CY, Khetchoumian K, Losson R, Stallcup MR. Transcriptional intermediary factor 1alpha mediates physical interaction and functional synergy between the coactivator-associated arginine methyltransferase 1 and glucocorticoid receptor-interacting protein 1 nuclear receptor coactivators. Mol Endocrinol. 2006 Jun;20(6):1276-86. Epub 2005 Dec 1. PMID:16322096 doi:10.1210/me.2005-0393
12. ↑ Cheng D, Cote J, Shaaban S, Bedford MT. The arginine methyltransferase CARM1 regulates the coupling of transcription and mRNA processing. Mol Cell. 2007 Jan 12;25(1):71-83. PMID:17218272 doi:http://dx.doi.org/10.1016/j.molcel.2006.11.019
13. ↑ Yue WW, Hassler M, Roe SM, Thompson-Vale V, Pearl LH. Insights into histone code syntax from structural and biochemical studies of CARM1 methyltransferase. EMBO J. 2007 Oct 17;26(20):4402-12. Epub 2007 Sep 20. PMID:17882261
14. ↑ Yadav N, Cheng D, Richard S, Morel M, Iyer VR, Aldaz CM, Bedford MT. CARM1 promotes adipocyte differentiation by coactivating PPARgamma. EMBO Rep. 2008 Feb;9(2):193-8. doi: 10.1038/sj.embor.7401151. Epub 2008 Jan 11. PMID:18188184 doi:http://dx.doi.org/10.1038/sj.embor.7401151
15. ↑ Feng Q, He B, Jung SY, Song Y, Qin J, Tsai SY, Tsai MJ, O'Malley BW. Biochemical control of CARM1 enzymatic activity by phosphorylation. J Biol Chem. 2009 Dec 25;284(52):36167-74. doi: 10.1074/jbc.M109.065524. Epub, 2009 Oct 20. PMID:19843527 doi:http://dx.doi.org/10.1074/jbc.M109.065524
16. ↑ Kim D, Lee J, Cheng D, Li J, Carter C, Richie E, Bedford MT. Enzymatic activity is required for the in vivo functions of CARM1. J Biol Chem. 2010 Jan 8;285(2):1147-52. Epub 2009 Nov 5. PMID:19897492 doi:http://dx.doi.org/M109.035865
17. ↑ Kuhn P, Chumanov R, Wang Y, Ge Y, Burgess RR, Xu W. Automethylation of CARM1 allows coupling of transcription and mRNA splicing. Nucleic Acids Res. 2011 Apr;39(7):2717-26. doi: 10.1093/nar/gkq1246. Epub 2010, Dec 7. PMID:21138967 doi:http://dx.doi.org/10.1093/nar/gkq1246