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

Cell Rep. 2018 Aug 14;24(7):1852-1864. doi: 10.1016/j.celrep.2018.07.046.

Abstract

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.

Keywords: Maf1; RNA polymerase III; adipogenesis; transcription.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Adipogenesis / genetics*
  • Animals
  • Butyrate Response Factor 1
  • Cell Differentiation
  • Embryoid Bodies / cytology
  • Embryoid Bodies / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Regulation, Developmental
  • Male
  • Mesoderm / cytology
  • Mesoderm / growth & development
  • Mesoderm / metabolism
  • Mice
  • Mice, Nude
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / metabolism
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Primary Cell Culture
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • RNA Polymerase III / genetics*
  • RNA Polymerase III / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Transcription, Genetic*
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism

Substances

  • Butyrate Response Factor 1
  • H19 long non-coding RNA
  • Maf1 protein, mouse
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Repressor Proteins
  • Wnt Proteins
  • Wnt6 protein, mouse
  • Zfp36l1 protein, mouse
  • RNA Polymerase III