Regulation of coactivator complex assembly and function by protein arginine methylation and demethylimination

Young Ho Lee, Scott A. Coonrod, W. Lee Kraus, Mary Anne Jelinek, Michael R. Stallcup

Research output: Contribution to journalArticle

165 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3611-3616
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number10
DOIs
StatePublished - Mar 8 2005

Keywords

  • Transcriptional regulation

ASJC Scopus subject areas

  • General

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