Regulation of Transcription by a Protein Methyltransferase

TLDR

The p160 family of coactivators (SRC‑1, GRIP1/TIF2, p/CIP) mediates nuclear hormone receptor–driven transcription, and their methylation may influence transcriptional regulation. CARM1, a protein that binds the C‑terminal region of p160 coactivators, acts as a secondary coactivator to enhance nuclear receptor transcription, can methylate histone H3, and requires an intact S‑adenosylmethionine binding domain for its methyltransferase and coactivator functions.

Abstract

The p160 family of coactivators, SRC-1, GRIP1/TIF2, and p/CIP, mediate transcriptional activation by nuclear hormone receptors. Coactivator-associated arginine methyltransferase 1 (CARM1), a previously unidentified protein that binds to the carboxyl-terminal region of p160 coactivators, enhanced transcriptional activation by nuclear receptors, but only when GRIP1 or SRC-1a was coexpressed. Thus, CARM1 functions as a secondary coactivator through its association with p160 coactivators. CARM1 can methylate histone H3 in vitro, and a mutation in the putative S-adenosylmethionine binding domain of CARM1 substantially reduced both methyltransferase and coactivator activities. Thus, coactivator-mediated methylation of proteins in the transcription machinery may contribute to transcriptional regulation.