Mat1 Inhibits Peroxisome Proliferator-Activated Receptor γ-Mediated Adipocyte Differentiation

Mammalian Cdk7, cyclin H, and Mat1 form the kinase submodule of transcription factor IIH (TFIIH) and have been considered ubiquitously expressed elements of the transcriptional machinery. Here we found that Mat1 and Cdk7 levels are undetectable in adipose tissues in vivo and downregulated during adipogenesis, where activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) acts as a critical differentiation switch. Using both Mat1(-/-) mouse embryonic fibroblasts and Cdk7 knockdown approaches, we show that the Cdk7 complex is an inhibitor of adipogenesis and is required for inactivation of PPAR gamma through the phosphorylation of PPAR gamma-S112. The results demonstrate that the Cdk7 submodule of TFIIH acts as a physiological roadblock to adipogenesis by inhibiting PPAR gamma activity. The observation that components of TFIIH are absent from transcriptionally active adipose tissue prompts a reevaluation of the ubiquitous nature of basal transcription factors in mammalian tissues.