期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 100, 期 11, 页码 6464-6468出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1232272100
关键词
arginine methylation; CARM1; p300; PABP; estrogen
资金
- NCI NIH HHS [CA16672, P30 CA016672] Funding Source: Medline
- NIDDK NIH HHS [DK62248-01, R56 DK062248, R01 DK062248] Funding Source: Medline
- NIEHS NIH HHS [P30 ES007784, ES07784] Funding Source: Medline
Arginine methylation has been implicated in the regulation of gene expression. The coactivator-associated arginine methyltransferase 1 (CARM1/PRMT4) binds the p160 family of steroid receptor coactivaltors (SRCs). This association enhances transcriptional activation by nuclear receptors. Here, we show that embryos with a targeted disruption of CARM1 are small in size and die perinatally. The methylation of two known CARM1 substrates, poly(A)-binding protein (PABP1) and the transcriptional cofactor p300, was abolished in knockout embryos and cells. However, CARM1-dependent methylation of histone H3 was not observed. Furthermore, estrogen-responsive gene expression was aberrant in Carm1(-/-) fibroblasts and embryos, thus emphasizing the role of arginine methylation as a transcription activation tag. These findings provide genetic evidence for the essential role of CARM1 in estrogen-mediated transcriptional activation.
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