BACKGROUND: Polycomb group (PcG) genes code for chromatin multiprotein complexes 
that are responsible for maintaining gene silencing of transcriptional programs 
during differentiation and in adult tissues. Despite the large amount of 
information on PcG function during development and cell identity homeostasis, 
little is known regarding the dynamics of PcG complexes and their role during 
terminal differentiation.
RESULTS: We show that two distinct polycomb repressive complex (PRC)2 complexes 
contribute to skeletal muscle cell differentiation: the PRC2-Ezh2 complex, which 
is bound to the myogenin (MyoG) promoter and muscle creatine kinase (mCK) 
enhancer in proliferating myoblasts, and the PRC2-Ezh1 complex, which replaces 
PRC2-Ezh2 on MyoG promoter in post-mitotic myotubes. Interestingly, the opposing 
dynamics of PRC2-Ezh2 and PRC2-Ezh1 at these muscle regulatory regions is 
differentially regulated at the chromatin level by Msk1 dependent methyl/phospho 
switch mechanism involving phosphorylation of serine 28 of the H3 histone 
(H3S28ph). While Msk1/H3S28ph is critical for the displacement of the PRC2-Ezh2 
complex, this pathway does not influence the binding of PRC2-Ezh1 on the 
chromatin. Importantly, depletion of Ezh1 impairs muscle differentiation and the 
chromatin recruitment of MyoD to the MyoG promoter in differentiating myotubes. 
We propose that PRC2-Ezh1 is necessary for controlling the proper timing of MyoG 
transcriptional activation and thus, in contrast to PRC2-Ezh2, is required for 
myogenic differentiation.
CONCLUSIONS: Our data reveal another important layer of epigenetic control 
orchestrating skeletal muscle cell terminal differentiation, and introduce a 
novel function of the PRC2-Ezh1 complex in promoter setting.