Publikationsdatum:
2012-10-24
Beschreibung:
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.
Print ISSN:
0305-1048
Digitale ISSN:
1362-4962
Thema:
Biologie
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