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Related Experiment Video

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Gene amplification during myogenic differentiation.

Ulrike Fischer1, Nicole Ludwig1, Abdulrahman Raslan2

  • 1Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany.

Oncotarget
|January 14, 2016
PubMed
Summary

Gene amplifications occur during mammalian cell differentiation, not just in tumors. This study observed gene copy number increases in mouse and human myoblasts, indicating amplification is a fundamental differentiation mechanism.

Keywords:
53BP1DSBgamma-H2AXmyoblastrereplication

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Area of Science:

  • Cell Biology
  • Genetics
  • Developmental Biology

Background:

  • Gene amplifications are typically associated with cancer cells and drug resistance.
  • Previous research indicated gene amplifications during neural progenitor cell differentiation.

Purpose of the Study:

  • To investigate gene amplifications during myoblast differentiation.
  • To determine if gene amplifications are a conserved mechanism in mammalian differentiation.

Main Methods:

  • Cultured mouse myoblasts (C2C12) and primary human myoblasts were induced to differentiate.
  • Gene copy number variations were analyzed over 7 days using quantitative methods.
  • Double-strand break markers (gamma-H2AX foci) and in vivo studies on mouse embryos were performed.

Main Results:

  • Increased copy numbers of CDK4, NUP133, and MYO18B genes were observed during mouse myoblast differentiation.
  • Gene amplifications, specifically CDK4 and NUP133, were also found in differentiating primary human myoblasts.
  • Amplified sequences were detected in the cytoplasm, suggesting nuclear export, and in vivo during mouse embryonic development (E11.5).

Conclusions:

  • Gene amplification is a fundamental mechanism during mammalian myoblast differentiation.
  • This process involves DNA damage and repair (gamma-H2AX foci).
  • Gene amplifications observed in myoblasts suggest a conserved role in mammalian development.