Abstract
The myogenic regulatory factors (MRFs) and myocyte enhancer factor 2 (MEF2) transcription factors have been extensively studied as key transcription factors that regulate myogenic gene expression. However, few reports on the molecular mechanism that modulates chromatin remodeling during skeletal muscle differentiation are available. We reported here that the expression of the H3-K9 methyltransferase Suv39h1 was decreased during myoblast differentiation. Ectopic expression of Suv39h1 could inhibit myoblast differentiation, increasing H3-K9 methylation levels, whereas knockdown of Suv39h1 stimulated myoblast differentiation. Furthermore, Suv39h1 interacted with MEF2C directly and inhibited MEF2 transcription activity in a dose-dependent manner. Together, our studies revealed a molecular mechanism wherein Suv39h1 modulated myogenic gene expression and activation during skeletal muscle differentiation.
Highlights
Skeletal muscle differentiation is a rigorous development program
We did not detect an opposite result from small interfering RNAs (siRNAs) interference experiments as we expected that the proliferation index was not significantly increased in si-Suv39h1 transfected cells compared to the control cells
Our observation indicated that Suv39h1 physically interacted with MEF2C and suppressed myocyte enhancer factor 2 (MEF2) target gene transactivation in a dose-dependent manner, and HP1 coordinated Suv39h1 to inhibit MEF2 target gene transactivation, whereas Western blot showed that HP1 did not coordinate Suv39h1 to down-regulate the expression of MEF2C
Summary
Genetic regulation in skeletal muscle differentiation primarily occurs at the transcription level [1]. Two key transcription factor families: myogenic regulatory factors (MRFs) and myocyte enhancer factor 2 (MEF2), are involved in this program and are required to activate downstream myogenic gene expression during muscle differentiation [2]. The MRF family includes Myf, Mrf, MyoD and myogenin. As master regulators of skeletal muscle differentiation, the MRF family functions through myoblast determination (Myf and MyoD) and differentiation (myogenin and Mrf4) [3,4,5]. MEF2 could perpetuate the differentiation program by regulating myogenic basic helix-loop-helix (bHLH) gene expression [8]. Histone covalent modification is an important epigenetic regulation mechanism that has essential function in chromatin structure regulation and gene expression.
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