Identification of ZNF395 as a novel modulator of adipogenesis

Abstract

Adipogenesis is the process of cell differentiation by which mesenchymal stem cells (MSC) become adipocytes. Investigating the transcriptional regulatory process during adipogenesis may provide strategies to prevent obesity and other metabolic disorders. In recent years, numerous zinc finger proteins (ZFPs) have been implicated in regulating differentiation and cell fate determination. To investigate the regulatory role of ZFPs involved in adipogenesis, we performed genome-wide microarray expression profiling of an adipogenesis time series. Particularly focusing on the transiently responsive ZFPs, we identified and characterized the functional role of ZNF395 in adipogenesis. A systematic ablation of the ZNF395 transcript during adipogenesis revealed 40% reduction of adipocytes when compared to control. Furthermore, the number of adipocytes as well as the expression of key adipocyte markers were greatly induced when MSC were co-transduced with ZNF395 and PPARG2. To further elucidate the functional role of ZNF395 during adipogenesis, we attempted to trans-differentiate human dermal fibroblasts with PPARG2. The test remarkably revealed that ZNF395 in conjunction with PPARG2 greatly induced adipogenesis from dermal fibroblasts when compared to PPARG2 alone. These loss and gain of function experiments firmly establish that ZNF395 coordinate the transcriptional regulatory pathway with PPARG2, which may be necessary for the genesis of adipocytes.