Maf1 and Repression of RNA Polymerase III-Mediated Transcription Drive Adipocyte Differentiation

Abstract

Summary: RNA polymerase (pol) III transcribes a variety of small untranslated RNAs involved in transcription, RNA processing, and translation. RNA pol III and its components are altered in various human developmental disorders, yet their roles in cell fate determination and development are poorly understood. Here we demonstrate that Maf1, a transcriptional repressor, promotes induction of mouse embryonic stem cells (mESCs) into mesoderm. Reduced Maf1 expression in mESCs and preadipocytes impairs adipogenesis, while ectopic Maf1 expression in Maf1-deficient cells enhances differentiation. RNA pol III repression by chemical inhibition or knockdown of Brf1 promotes adipogenesis. Altered RNA pol III-dependent transcription produces select changes in mRNAs with a significant enrichment of adipogenic gene signatures. Furthermore, RNA pol III-mediated transcription positively regulates long non-coding RNA H19 and Wnt6 expression, established adipogenesis inhibitors. Together, these studies reveal an important and unexpected function for RNA pol III-mediated transcription and Maf1 in mesoderm induction and adipocyte differentiation. : Maf1 and RNA pol III transcription repression play a key role in cell fate determination by promoting mesoderm induction and adipocyte differentiation. Chen et al. show that alterations in RNA pol III transcription produce select changes in adipogenic genes, and inhibitory factors including Wnt6 and H19lnc RNA, to regulate adipogenesis. Keywords: RNA polymerase III, Maf1, transcription, adipogenesis