title: Canonical Wnt signalling regulates nuclear export of Setdb1 during skeletal muscle terminal differentiation.
abstract: The histone 3 lysine 9 methyltransferase Setdb1 is essential for both stem cell pluripotency and terminal differentiation of different cell types. To shed light on the roles of Setdb1 in these mutually exclusive processes, we used mouse skeletal myoblasts as a model of terminal differentiation.Ex vivostudies on isolated single myofibres showed that Setdb1 is required for adult muscle stem cells expansion following activation.In vitrostudies in skeletal myoblasts confirmed that Setdb1 suppresses terminal differentiation. Genomic binding analyses showed a release of Setdb1 from selected target genes upon myoblast terminal differentiation, concomitant to a nuclear export of Setdb1 to the cytoplasm. Both genomic release and cytoplasmic Setdb1 relocalisation during differentiation were dependent on canonical Wnt signalling. Transcriptomic assays in myoblasts unravelled a significant overlap between Setdb1 and Wnt3a regulated genetic programmes. Together, our findings revealed Wnt-dependent subcellular relocalisation of Setdb1 as a novel mechanism regulating Setdb1 functions and myogenesis.
authors: Centre National de la Recherche Scientifique CNRS-Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate UMR7216 , Paris, France.
authors: Sophie
authors: S
authors: Beyer
authors: Centre National de la Recherche Scientifique CNRS-Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate UMR7216 , Paris, France.
authors: Julien
authors: J
authors: Pontis
authors: Institut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS) UMR8104, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1016, Paris, France.
authors: Elija
authors: E
authors: Schirwis
authors: Centre National de la Recherche Scientifique CNRS-Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate UMR7216 , Paris, France.
authors: Valentine
authors: V
authors: Battisti
authors: Institut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS) UMR8104, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1016, Paris, France.
authors: Anja
authors: A
authors: Rudolf
authors: Institut Cochin, Université Paris-Descartes, Centre National de la Recherche Scientifique (CNRS) UMR8104, Paris, France; Institut National de la Santé et de la Recherche Médicale (INSERM) U1016, Paris, France.
authors: Fabien
authors: F
authors: Le Grand
authors: Centre National de la Recherche Scientifique CNRS-Université Paris Diderot, Sorbonne Paris Cité, Epigenetics and Cell Fate UMR7216 , Paris, France.
authors: Slimane
authors: S
authors: Ait-Si-Ali
keywords: SETDB1/ESET/KMT1E; Wnt signalling; differentiation; lysine; methyltransferase; muscle