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 CBFβ. CBF was originally described as a regulator of hematopoiesis. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that CBF is involved in the control of skeletal muscle terminal differentiation. Indeed, downregulation of either Runx1 or CBFβ protein level accelerates cell cycle exit and muscle terminal differentiation. Conversely, overexpression of CBFβ 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 HP1β. When overexpressed, CBFβ induced an inhibition of activating histone modification marks concomitant with an increase in repressive modifications at MyoD target promoters. CONCLUSIONS/SIGNIFICANCE: Taken together, our data show a new role for Runx1/CBFβ in the control of the proliferation/differentiation in skeletal myoblasts.