The Febs Journal

Title : p53 mediated regulation ofcoactivator associated arginine methyltransferase 1 (CARM1) expression iscritical for suppression of adipogenesis.
Abstract : Coactivator-associated arginine methyltransferase 1 (CARM1/PRMT4) is a type I arginine methyltransferase that mediates transcriptional activation via methylation of histone H3 on R17, R26, and R42. CARM1 is also a coactivator of transcription of various transcription factors such as NF-kB, MEF2C, β-catenin, p53, PPAR-gamma etc. CARM1 has been functionally implicated in maintenance of pluripotency, cellular differentiation, and tumorigenesis; where its expression status plays an important role. Although its expression has been shown to be regulated by a few miRNAs in different contexts at post-transcriptional level, transcriptional regulation of CARM1 gene is still unexplored. In this report we demonstrate that CARM1 is a p53 responsive gene, where p53 could suppress CARM1 promoter-driven luciferase expression. CARM1 gene expression was found to be repressed by p53 in 3T3L1 preadipocytes when activated with Nutlin-3a treatment. Ectopic overexpression of CARM1 could rescue inhibitory effect of p53 on adipogenesis, suggesting a role of p53-CARM1 axis of regulation operational in the context of adipocyte differentiation. p53 and CARM1 showed antagonistic regulatory influence on PPAR-gamma expression; which suggests that p53-mediated suppression of adipogenesis could be partly via repression of CARM1 expression. Taken together these observations provide convincing mechanistic explanation for p53 function in the context of adipocyte differentiation process.
Authors : Behera AK, Bhattacharya A, Vasudevan M, Kundu TK.

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