Regulation of transcription by a protein methyltransferase.
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.
Chen
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Department of Pathology HMR 301, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA.
Ma
H
H
Hong
H
H
Koh
S S
SS
Huang
S M
SM
Schurter
B T
BT
Aswad
D W
DW
Stallcup
M R
MR
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D056921:Nuclear Receptor Coactivator 3; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D006657:Histones; C498002:Ncoa2 protein, mouse; D051958:Nuclear Receptor Coactivator 2; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; D051548:Histone Acetyltransferases; C538861:Ncoa1 protein, mouse; C538867:Ncoa3 protein, mouse; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3