A new role for sterol regulatory element binding protein 1 transcription factors in the regulation of muscle mass and muscle cell differentiation

Mol Cell Biol. 2010 Mar;30(5):1182-98. doi: 10.1128/MCB.00690-09. Epub 2009 Dec 22.


The role of the transcription factors sterol regulatory element binding protein 1a (SREBP-1a) and SREBP-1c in the regulation of cholesterol and fatty acid metabolism has been well studied; however, little is known about their specific function in muscle. In the present study, analysis of recent microarray data from muscle cells overexpressing SREBP1 suggested that they may play a role in the regulation of myogenesis. We then demonstrated that SREBP-1a and -1c inhibit myoblast-to-myotube differentiation and also induce in vivo and in vitro muscle atrophy. Furthermore, we have identified the transcriptional repressors BHLHB2 and BHLHB3 as mediators of these effects of SREBP-1a and -1c in muscle. Both repressors are SREBP-1 target genes, and they affect the expression of numerous genes involved in the myogenic program. Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Down-Regulation
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Muscle Development / genetics
  • Muscle Development / physiology
  • Muscle Fibers, Skeletal / cytology*
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle, Skeletal / growth & development*
  • Muscle, Skeletal / metabolism*
  • Muscular Atrophy / etiology
  • Myoblasts, Skeletal / cytology
  • Myoblasts, Skeletal / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism*


  • BHLHE40 protein, human
  • BHLHE41 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • Homeodomain Proteins
  • Recombinant Proteins
  • Repressor Proteins
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1