期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 14, 页码 -出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.164574
关键词
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资金
- National Institutes of Health [HL54737]
- Direccion General de Asuntos del Personal Academico
- Universidad Nacional Autonoma de Mexico [IX230104, IN209403, IN214407]
- Consejo Nacional de Ciencia y Tecnologia [42653-Q, 58767]
- Third World Academy of Sciences [01-055 RG/BIO/LA]
- J. David Gladstone Institutes
- California Institute of Regenerative Medicine
CTCF nuclear factor regulates many aspects of gene expression, largely as a transcriptional repressor or via insulator function. Its roles in cellular differentiation are not clear. Here we show an unexpected role for CTCF in myogenesis. Ctcf is expressed in myogenic structures during mouse and zebrafish development. Gain-and loss-of-function approaches in C2C12 cells revealed CTCF as a modulator of myogenesis by regulating muscle-specific gene expression. We addressed the functional connection between CTCF and myogenic regulatory factors (MRFs). CTCF enhances the myogenic potential of MyoD and myogenin and establishes direct interactions with MyoD, indicating that CTCF regulates MRF-mediated muscle differentiation. Indeed, CTCF modulates functional interactions between MyoD and myogenin in co-activation of muscle-specific gene expression and facilitates MyoD recruitment to a muscle-specific promoter. Finally, ctcf loss-of-function experiments in zebrafish embryos revealed a critical role of CTCF in myogenic development and linked CTCF to broader aspects of development via regulation of Wnt signaling. We conclude that CTCF modulates MRF functional interactions in the orchestration of myogenesis.
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