Abstract
BackgroundCore 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 FindingsHere 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/SignificanceTaken together, our data show a new role for Runx1/CBFβ in the control of the proliferation/differentiation in skeletal myoblasts.
Highlights
IntroductionRunx (for Runt-related transcription factor 1, known as AML1 for Acute Myeloid Leukemia 1, CBFA2 or PEPB2aB) belongs to a family of highly homologous heterodimeric transcription factors named Core Binding Factors or CBF (reviewed in: [1])
Runx1 belongs to a family of highly homologous heterodimeric transcription factors named Core Binding Factors or CBF
MyoD protein complex composition was analyzed by mass spectrometry (MS) and western blot (WB)
Summary
Runx (for Runt-related transcription factor 1, known as AML1 for Acute Myeloid Leukemia 1, CBFA2 or PEPB2aB) belongs to a family of highly homologous heterodimeric transcription factors named Core Binding Factors or CBF (reviewed in: [1]). In addition to the Runx subunit which binds DNA directly, CBF is composed of a non-DNA-binding subunit named CBFbeta (CBFb) [2]. Genetic studies showed that Runx is essential in the developing murine embryo for definitive hematopoiesis of all lineages [5,6]. Core Binding Factor or CBF is a transcription factor composed of two subunits, Runx1/AML-1 and CBF beta or CBFb. CBF was originally described as a regulator of hematopoiesis
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