Specific protein methylation defects and gene expression perturbations in coactivator-associated arginine methyltransferase 1-deficient mice.
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.
Yadav
Neelu
N
Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, P.O. Box 389, Smithville 78957, USA.
Lee
Jaeho
J
Kim
Jeesun
J
Shen
Jianjun
J
Hu
Mickey C-T
MC
Aldaz
C Marcelo
CM
Bedford
Mark T
MT
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D050881:E1A-Associated p300 Protein; D015870:Gene Expression; D005804:Genes, Lethal; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D039122:Poly(A)-Binding Protein I / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism
D009687:Nuclear Proteins; D039122:Poly(A)-Binding Protein I; D015534:Trans-Activators; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse