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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Cell Line
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Histone Acetyltransferases
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Histones / metabolism
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Methylation
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Mice
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Molecular Sequence Data
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Mutation
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Nuclear Receptor Coactivator 1
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Nuclear Receptor Coactivator 2
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Nuclear Receptor Coactivator 3
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Protein-Arginine N-Methyltransferases / chemistry
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Protein-Arginine N-Methyltransferases / genetics
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Protein-Arginine N-Methyltransferases / metabolism*
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Receptors, Androgen / metabolism
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Receptors, Estrogen / metabolism
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Receptors, Thyroid Hormone / metabolism
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Recombinant Fusion Proteins / metabolism
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Signal Transduction
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Trans-Activators / metabolism*
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Transcription Factors / metabolism
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Transcriptional Activation*
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Transfection
Substances
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Histones
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Ncoa2 protein, mouse
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Nuclear Receptor Coactivator 2
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Receptors, Androgen
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Receptors, Estrogen
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Receptors, Thyroid Hormone
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Recombinant Fusion Proteins
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Trans-Activators
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Transcription Factors
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Protein-Arginine N-Methyltransferases
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coactivator-associated arginine methyltransferase 1
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Histone Acetyltransferases
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Ncoa1 protein, mouse
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Ncoa3 protein, mouse
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Nuclear Receptor Coactivator 1
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Nuclear Receptor Coactivator 3