Science · 1999 · 1.2K citations · 16 references
Life SciencesGeneticsMolecular BiologyGene ExpressionGene RegulationTranscriptional RegulationChromatinHistone ModificationsNuclear Receptor SignalingNuclear ReceptorsTranscription FactorsTranscriptional ControlHistone Arginine MethylationHistone MethylationHormone-receptor CoactivatorsMethylation DomainsNuclear Hormone ReceptorsNuclear Receptor CoactivatorsNuclear Receptor Transcriptional RegulationTranscriptional Activation
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.
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.
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Hao Hong, Kulwant K. Kohli, Alpa Trivedi et al. · Proceedings of the National Academy of Sciences · 1996 · 705 citations