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Proc Natl Acad Sci U S A. 2003 May 27;100(11):6464-8. Epub 2003 May 19.

Specific protein methylation defects and gene expression perturbations in coactivator-associated arginine methyltransferase 1-deficient mice.

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  • 1Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, P.O. Box 389, Smithville 78957, USA.

Abstract

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 coactivators (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.

PMID:
12756295
[PubMed - indexed for MEDLINE]
PMCID:
PMC164469
Free PMC Article

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