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TFE3 inhibits myoblast differentiation in C2C12 cells via down-regulating gene expression of myogenin

Ayano Naka1, Kaoruko Tada Iida, Yoshimi Nakagawa

  • 1Doctoral Program of Sports Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.

Biochemical and Biophysical Research Communications
|December 6, 2012
PubMed

Insights

Transcription factor E3 (TFE3) inhibits skeletal muscle cell differentiation by suppressing myogenin. Knocking down TFE3 promotes this process, revealing TFE3

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Transcription factor E3 (TFE3) is a basic helix-loop-helix protein involved in osteoclast and melanocyte biology.
  • Previous research highlighted TFE3's metabolic influence on insulin in liver and skeletal muscle.
  • The specific role of TFE3 in skeletal muscle cell differentiation remained largely unexplored.

Purpose of the Study:

  • To investigate the novel role of TFE3 in regulating skeletal muscle cell differentiation.
  • To elucidate the molecular mechanisms by which TFE3 affects myogenesis.
  • To determine TFE3's impact on the expression of key muscle regulatory factors (MRFs).

Main Methods:

  • Adenovirus-mediated overexpression and knockdown of TFE3 in C2C12 myoblasts.
  • Assessment of myogenic differentiation markers and gene expression.
  • Luciferase reporter assays and electrophoretic mobility shift assays (EMSA) for promoter analysis.

Main Results:

  • TFE3 overexpression significantly inhibited myogenic differentiation of C2C12 cells.
  • TFE3 suppressed the expression of MRFs, including MyoD and myogenin.
  • TFE3 knockdown promoted myoblast differentiation and increased MRF expression.
  • TFE3 directly binds to the myogenin promoter's E-box (E2) and negatively regulates its activity.

Conclusions:

  • TFE3 plays a critical inhibitory role in skeletal muscle cell differentiation.
  • Transcriptional suppression of myogenin expression by TFE3 is a key mechanism underlying its effect on myogenesis.
  • TFE3 acts as a negative regulator of myoblast differentiation.

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