Specific protein methylation defects and gene expression perturbations in coactivator-associated arginine methyltransferase 1-deficient mice
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.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- May 2003
- DOI:
- 10.1073/pnas.1232272100
- Bibcode:
- 2003PNAS..100.6464Y
- Keywords:
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- CELL BIOLOGY