Chromatin remodeling protein SMAR1 regulates adipogenesis by modulating the expression of PPARγ

Abstract

Adipogenesis is described as the process of conversion of pre-adipocytes into differentiated lipid-laden adipocytes. Adipogenesis is known to be regulated by a myriad of transcription factors and co-regulators. However, there is a dearth of information regarding the mechanisms that regulate these transcription factors and hence control adipogenesis. PPARγ is the master transcriptional regulator of adipogenesis and its expression is essential for adipocyte differentiation. Herein, we identified that scaffold/matrix attachment region-binding protein 1 (SMAR1) negatively regulates adipogenesis. We observed that SMAR1 gets downregulated during adipocyte differentiation and knockdown of SMAR1 promotes lipid accumulation and adipocyte differentiation. Mechanistically, we have shown that SMAR1 suppresses PPARγ through recruitment of the HDAC1/mSin3a repressor complex to the PPARγ promoter. We further identified cell division cycle 20 (cdc20) mediated proteasomal degradation of SMAR1 during adipogenesis. Moreover, knockdown of cdc20 resulted in stabilization of SMAR1 and a reduction in adipocyte differentiation. Taken together, our observations suggest that SMAR1 functions as a negative regulator of adipogenesis by inhibiting PPARγ expression in differentiating adipocytes.