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Inhibition of in vitro myogenic differentiation by cellular transcription factor E2F1

J Wang1, K Helin, P Jin

  • 1Department of Cardiology, Children's Hospital, Boston, Massachusetts 02135, USA.

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|October 1, 1995
PubMed

Insights

Cellular transcription factor E2F1 (E2F1) normally down-regulates during myocyte differentiation. Overexpression of E2F1 inhibits muscle cell differentiation by preventing cell cycle exit and repressing myogenin expression.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Developmental Biology

Background:

  • Terminal differentiation of cultured myocytes necessitates cell cycle withdrawal.
  • Oncogene overexpression in myoblasts can impede in vitro myogenesis.

Purpose of the Study:

  • To investigate the role of the cellular transcription factor E2F1 in myogenic differentiation.
  • To determine if E2F1 down-regulation is essential for myogenesis.

Main Methods:

  • Studied E2F1 expression during differentiation of C2C12 myocytes.
  • Examined the effects of deregulated E2F1 expression on myogenesis in C2C12 cells.
  • Assessed myogenin and cyclin D1 expression levels.

Main Results:

  • E2F1 expression was irreversibly down-regulated during C2C12 myocyte differentiation.
  • Deregulated E2F1 expression inhibited myogenesis, repressed myogenin, and elevated cyclin D1.
  • E2F1-overexpressing myocytes failed to exit the cell cycle under differentiation conditions.

Conclusions:

  • E2F1 functions as an oncogene, inhibiting myogenic differentiation.
  • E2F1 down-regulation is a required event for successful myogenic differentiation.

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