Ret finger protein inhibits muscle differentiation by modulating serum response factor and enhancer of polycomb1

H. J. Kee, J. R. Kim, H. Joung, N. Choe, S. E. Lee, G. H. Eom, J. C. Kim, S. H. Geyer, M. Jijiwa, T. Kato, K. Kawai, W. J. Weninger, S. B. Seo, K. I. Nam, M. H. Jeong, M. Takahashi, H. Kook

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Abstract

Skeletal myogenesis is precisely regulated by multiple transcription factors. Previously, we demonstrated that enhancer of polycomb 1 (Epc1) induces skeletal muscle differentiation by potentiating serum response factor (SRF)-dependent muscle gene activation. Here, we report that an interacting partner of Epc1, ret finger protein (RFP), blocks skeletal muscle differentiation. Our findings show that RFP was highly expressed in skeletal muscles and was downregulated during myoblast differentiation. Forced expression of RFP delayed myoblast differentiation, whereas knockdown enhanced it. Epc1-induced enhancements of SRF-dependent multinucleation, transactivation of the skeletal α-actin promoter, binding of SRF to the serum response element, and muscle-specific gene induction were blocked by RFP. RFP interfered with the physical interaction between Epc1 and SRF. Muscles from rfp knockout mice (Rfp -/-) mice were bigger than those from wild-type mice, and the expression of SRF-dependent muscle-specific genes was upregulated. Myotube formation and myoblast differentiation were enhanced in Rfp -/- mice. Taken together, our findings highlight RFP as a novel regulator of muscle differentiation that acts by modulating the expression of SRF-dependent skeletal muscle-specific genes.

Original languageEnglish
Pages (from-to)121-131
Number of pages11
JournalCell Death and Differentiation
Volume19
Issue number1
DOIs
Publication statusPublished - 01-01-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Kee, H. J., Kim, J. R., Joung, H., Choe, N., Lee, S. E., Eom, G. H., Kim, J. C., Geyer, S. H., Jijiwa, M., Kato, T., Kawai, K., Weninger, W. J., Seo, S. B., Nam, K. I., Jeong, M. H., Takahashi, M., & Kook, H. (2012). Ret finger protein inhibits muscle differentiation by modulating serum response factor and enhancer of polycomb1. Cell Death and Differentiation, 19(1), 121-131. https://doi.org/10.1038/cdd.2011.72