title: Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2 and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells.
abstract: 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.
authors: Dulbecco Telethon Institute, IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Oncology, University of Cambridge, Cancer Research UK Cambridge Research Institute, Cambridge, UK.
authors: Lovorka
authors: L
authors: Stojic
authors: Dulbecco Telethon Institute, IRCCS Fondazione Santa Lucia, Rome, Italy.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors: Zuzana
authors: Z
authors: Jasencakova
authors: Dulbecco Telethon Institute, IRCCS Fondazione Santa Lucia, Rome, Italy.
authors: Carolina
authors: C
authors: Prezioso
authors: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Alexandra
authors: A
authors: Stützer
authors: Dulbecco Telethon Institute, IRCCS Fondazione Santa Lucia, Rome, Italy.|Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy.
authors: Beatrice
authors: B
authors: Bodega
authors: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.|Department of Experimental Oncology, European Institute of Oncology, c/o IFOM-IEO Campus, Milan, Italy.
authors: Diego
authors: D
authors: Pasini
authors: Leibniz-Institut fuer Molekulare Pharmakologie (FMP), Department of Chemical Biology/Protein Chemistry, Berlin, Germany.
authors: Rebecca
authors: R
authors: Klingberg
authors: Dulbecco Telethon Institute, IRCCS Fondazione Santa Lucia, Rome, Italy.|Universitè Paris Diderot Paris 7, CNRS, Paris, France.
authors: Chiara
authors: C
authors: Mozzetta
authors: Curie Institute, Unité de Génétique et Biologie du Développement, Paris, France.
authors: Raphael
authors: R
authors: Margueron
authors: Dulbecco Telethon Institute, IRCCS Fondazione Santa Lucia, Rome, Italy.|The Sanford Burnham Institute, La Jolla, CA, USA.
authors: Pier Lorenzo
authors: PL
authors: Puri
authors: Leibniz-Institut fuer Molekulare Pharmakologie (FMP), Department of Chemical Biology/Protein Chemistry, Berlin, Germany.
authors: Dirk
authors: D
authors: Schwarzer
authors: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark.
authors: Kristian
authors: K
authors: Helin
authors: Laboratory of Chromatin Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors: Wolfgang
authors: W
authors: Fischle
authors: Dulbecco Telethon Institute, IRCCS Fondazione Santa Lucia, Rome, Italy.
authors: Valerio
authors: V
authors: Orlando