The core binding factor CBF negatively regulates skeletal muscle terminal differentiation.
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.
Philipot
Ophélie
O
Institut André Lwoff, FRE2944, CNRS and Université Paris-Sud, Villejuif, France.
Joliot
Véronique
V
Ait-Mohamed
Ouardia
O
Pellentz
Céline
C
Robin
Philippe
P
Fritsch
Lauriane
L
Ait-Si-Ali
Slimane
S
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
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