title: CTCF promotes muscle differentiation by modulating the activity of myogenic regulatory factors.
abstract: 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.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Delgado-Olguín
authors.forename: Koroboshka
authors.initials: K
authors.lastname: Brand-Arzamendi
authors.forename: Ian C
authors.initials: IC
authors.lastname: Scott
authors.forename: Benno
authors.initials: B
authors.lastname: Jungblut
authors.forename: Didier Y
authors.initials: DY
authors.lastname: Stainier
authors.forename: Benoit G
authors.initials: BG
authors.lastname: Bruneau
authors.forename: Félix
authors.initials: F
authors.lastname: Recillas-Targa
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004622:Embryo, Mammalian / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D051379:Mice; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019170:Somites / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000076246:CCCTC-Binding Factor; C000619698:Ctcf protein, mouse; D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D051153:Wnt Proteins; C092568:Wnt11 protein, zebrafish; D029961:Zebrafish Proteins