Ablation of PRMT6 reveals a role as a negative transcriptional regulator of the p53 tumor suppressor.
Nucleic Acids Res
; 40(19): 9513-21, 2012 Oct.
Article
en En
| MEDLINE
| ID: mdl-22904064
ABSTRACT
Arginine methylation of histones is a well-known regulator of gene expression. Protein arginine methyltransferase 6 (PRMT6) has been shown to function as a transcriptional repressor by methylating the histone H3 arginine 2 [H3R2(me2a)] repressive mark; however, few targets are known. To define the physiological role of PRMT6 and to identify its targets, we generated PRMT6(-/-) mouse embryo fibroblasts (MEFs). We observed that early passage PRMT6(-/-) MEFs had growth defects and exhibited the hallmarks of cellular senescence. PRMT6(-/-) MEFs displayed high transcriptional levels of p53 and its targets, p21 and PML. Generation of PRMT6(-/-); p53(-/-) MEFs prevented the premature senescence, suggesting that the induction of senescence is p53-dependent. Using chromatin immunoprecipitation assays, we observed an enrichment of PRMT6 and H3R2(me2a) within the upstream region of Trp53. The PRMT6 association and the H3R2(me2a) mark were lost in PRMT6(-/-) MEFs and an increase in the H3K4(me3) activator mark was observed. Our findings define a new regulator of p53 transcriptional regulation and define a role for PRMT6 and arginine methylation in cellular senescence.
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Proteína-Arginina N-Metiltransferasas
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Transcripción Genética
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Regulación de la Expresión Génica
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Proteína p53 Supresora de Tumor
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Proteínas de Drosophila
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2012
Tipo del documento:
Article