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PMID: 12756295 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 11 ·2003-05-27 ·Pages 6464-8

Yadav N, Lee J, Kim J, Shen J, Hu MC, Aldaz CM, Bedford MT

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.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Cells, Cultured E1A-Associated p300 Protein Gene Expression Genes, Lethal Methylation Mice Mice, Knockout Molecular Sequence Data Nuclear Proteins/metabolism Poly(A)-Binding Protein I/metabolism Protein-Arginine N-Methyltransferases/genetics,metabolism Trans-Activators/metabolism
Chemicals
Nuclear Proteins Poly(A)-Binding Protein I Trans-Activators Protein-Arginine N-Methyltransferases coactivator-associated arginine methyltransferase 1 E1A-Associated p300 Protein Ep300 protein, mouse
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Yadav Neelu
Department of Carcinogenesis, University of Texas M. D. Anderson Cancer Center, P.O. Box 389, Smithville 78957, USA.
Lee Jaeho
Kim Jeesun
Shen Jianjun
Hu Mickey C-T
Aldaz C Marcelo
Bedford Mark T
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1232272100
Published
2003-05-27
Epub
2003-00-19
Pages
6464-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC164469
Subset
IM
Grants
NIDDK NIH HHS · R01 DK062248 · United States
NIDDK NIH HHS · R56 DK062248 · United States
NCI NIH HHS · P30 CA016672 · United States
NCI NIH HHS · CA16672 · United States
NIDDK NIH HHS · DK62248-01 · United States
NIEHS NIH HHS · P30 ES007784 · United States
NIEHS NIH HHS · ES07784 · United States
External Links
PubMed source DOI: 10.1073/pnas.1232272100 PMC Full Text View journal details
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