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

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.

Pubmed ID: 15731352

Authors

  • Lee YH
  • Coonrod SA
  • Kraus WL
  • Jelinek MA
  • Stallcup MR

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

March 8, 2005

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK 55274
  • Agency: NIDDK NIH HHS, Id: DK 58110
  • Agency: NICHD NIH HHS, Id: HD 38353

Mesh Terms

  • Arginine
  • Binding Sites
  • Humans
  • Methylation
  • Nuclear Proteins
  • Nuclear Receptor Coactivator 2
  • Protein Conformation
  • Protein-Arginine N-Methyltransferases
  • Receptors, Estrogen
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Activation