Gene amplification during myogenic differentiation
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Ulrike Fischer1, Nicole Ludwig1, Abdulrahman Raslan2, Carola Meier2, Eckart Meese1
1Department of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany
2Department of Anatomy and Cell Biology, Saarland University, 66421 Homburg/Saar, Germany
Ulrike Fischer, e-mail: [email protected]
Keywords: myoblast, rereplication, gamma-H2AX, 53BP1, DSB
Received: July 10, 2015 Accepted: January 02, 2016 Published: January 08, 2016
Gene amplifications are mostly an attribute of tumor cells and drug resistant cells. Recently, we provided evidence for gene amplifications during differentiation of human and mouse neural progenitor cells. Here, we report gene amplifications in differentiating mouse myoblasts (C2C12 cells) covering a period of 7 days including pre-fusion, fusion and post-fusion stages. After differentiation induction we found an increase in copy numbers of CDK4 gene at day 3, of NUP133 at days 4 and 7, and of MYO18B at day 4. The amplification process was accompanied by gamma-H2AX foci that are indicative of double stand breaks. Amplifications during the differentiating process were also found in primary human myoblasts with the gene CDK4 and NUP133 amplified both in human and mouse myoblasts. Amplifications of NUP133 and CDK4 were also identified in vivo on mouse transversal cryosections at stage E11.5. In the course of myoblast differentiation, we found amplifications in cytoplasm indicative of removal of amplified sequences from the nucleus. The data provide further evidence that amplification is a fundamental mechanism contributing to the differentiation process in mammalians.
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