First Author | Yadav N | Year | 2003 |
Journal | Proc Natl Acad Sci U S A | Volume | 100 |
Issue | 11 | Pages | 6464-8 |
PubMed ID | 12756295 | Mgi Jnum | J:83623 |
Mgi Id | MGI:2662764 | Doi | 10.1073/pnas.1232272100 |
Citation | Yadav N, et al. (2003) Specific protein methylation defects and gene expression perturbations in coactivator-associated arginine methyltransferase 1-deficient mice. Proc Natl Acad Sci U S A 100(11):6464-8 |
abstractText | 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. |