title: The core binding factor CBF negatively regulates skeletal muscle terminal differentiation.
abstract: BACKGROUND
  Core Binding Factor or CBF is a transcription factor composed of two subunits, Runx1/AML-1 and CBF beta or CBFbeta. CBF was originally described as a regulator of hematopoiesis.
  
  
  RESULTS
  Here we show that CBF is involved in the control of skeletal muscle terminal differentiation. Indeed, downregulation of either Runx1 or CBFbeta protein level accelerates cell cycle exit and muscle terminal differentiation. Conversely, overexpression of CBFbeta in myoblasts slows terminal differentiation. CBF interacts directly with the master myogenic transcription factor MyoD, preferentially in proliferating myoblasts, via Runx1 subunit. In addition, we show a preferential recruitment of Runx1 protein to MyoD target genes in proliferating myoblasts. The MyoD/CBF complex contains several chromatin modifying enzymes that inhibits MyoD activity, such as HDACs, Suv39h1 and HP1beta. When overexpressed, CBFbeta induced an inhibition of activating histone modification marks concomitant with an increase in repressive modifications at MyoD target promoters.
  
  
  CONCLUSIONS
  Taken together, our data show a new role for Runx1/CBFbeta in the control of the proliferation/differentiation in skeletal myoblasts.
authors.affiliation: Institut André Lwoff, FRE2944, CNRS and Université Paris-Sud, Villejuif, France.
authors.forename: Ophélie
authors.initials: O
authors.lastname: Philipot
authors.forename: Véronique
authors.initials: V
authors.lastname: Joliot
authors.forename: Ouardia
authors.initials: O
authors.lastname: Ait-Mohamed
authors.forename: Céline
authors.initials: C
authors.lastname: Pellentz
authors.forename: Philippe
authors.initials: P
authors.lastname: Robin
authors.forename: Lauriane
authors.initials: L
authors.lastname: Fritsch
authors.forename: Slimane
authors.initials: S
authors.lastname: Ait-Si-Ali
mesh_terms: D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D000090266:Chromobox Protein Homolog 5; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D050658:Core Binding Factor beta Subunit / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D050660:Core Binding Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding; D034622:RNA Interference; D014162:Transfection
chemical_list: C000715593:CBX1 protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D050658:Core Binding Factor beta Subunit; D050660:Core Binding Factors; D017570:MyoD Protein; D000090266:Chromobox Protein Homolog 5