| Title: |
Ablation of PRMT6 reveals a role as a negative transcriptional regulator of the p53 tumor suppressor |
| Authors: |
Neault, Mathieu; Mallette, Frédérick A.; Vogel, Gillian; Michaud-Levesque, Jonathan; Richard, Stéphane |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2012 |
| Collection: |
HighWire Press (Stanford University) |
| Subject Terms: |
Gene Regulation; Chromatin and Epigenetics |
| Description: |
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. |
| Document Type: |
text |
| File Description: |
text/html |
| Language: |
English |
| Relation: |
http://nar.oxfordjournals.org/cgi/content/short/40/19/9513; http://dx.doi.org/10.1093/nar/gks764 |
| DOI: |
10.1093/nar/gks764 |
| Availability: |
http://nar.oxfordjournals.org/cgi/content/short/40/19/9513; https://doi.org/10.1093/nar/gks764 |
| Rights: |
Copyright (C) 2012, Oxford University Press |
| Accession Number: |
edsbas.8B42ED77 |
| Database: |
BASE |