Tumor suppressor p53 regulate Adipogenesis Epigenetically

Tumor suppressor p53 regulate Adipogenesis Epigenetically

In this study our group have discovered that p53 mediated regulation of expression of CARM1, a well-known transcriptional coactivator and arginine methyltransferase, negatively impacts fate of adipocyte differentiation. We demonstrated that p53 gets recruited to CARM1 promoter and represses its expression. When CARM1 expression is not repressed by p53, CARM1 induces and maintains PPARγ2 expression, which is essential for normal adipogenesis. Further transcriptome analysis and gene network modeling revealed multiple pathways along with lipid biogenesis pathway also to be modulated by p53 in preadipocytes. The experimental evidences on p53 mediated repression of CARM1 expression seem to bridge the mechanistic gap within the regulatory influence of p53 on PPAR-γ expression in adipocytes. This would illuminate our understanding on metabolism of glucose and lipid at organismal level with a molecular basis and allow to address obesity and associative complications such as diabetes with better scientific preparedness.