P53 mediated regulation of Coactivator associated arginine methyltransferase 1 (CARM1) expression is critical 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 acts as 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 the present study 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.Support or Funding InformationTKK is recipient of JC Bose fellowship from Dept. of Science and technology, Govt. of India (SR/S2/JCB‐28/2010). AKB is a research associate of JNCASR. AB is a senior research fellow of UGC, India. This work was supported by funding from Dept. of Biotchnology, Govt. of India (BT/01/CEIB/10/III/01) and JNCASR, India.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.