The Histone Variant MacroH2A1 Regulates Key Genes for Myogenic Cell Fusion in a Splice-Isoform Dependent Manner - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cells Année : 2020

The Histone Variant MacroH2A1 Regulates Key Genes for Myogenic Cell Fusion in a Splice-Isoform Dependent Manner

Sarah Hurtado-Bagès
  • Fonction : Auteur
Melanija Posavec Marjanovic
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  • PersonId : 1085344
Vanesa Valero
  • Fonction : Auteur
  • PersonId : 1085345
Roberto Malinverni
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  • PersonId : 1085346
David Corujo
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  • PersonId : 1085347
Philippe Bouvet
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  • PersonId : 859839
Kerstin Bystricky
Marcus Buschbeck
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  • PersonId : 1085348

Résumé

MacroH2A histone variants have functions in differentiation, somatic cell reprogramming and cancer. However, at present, it is not clear how macroH2As affect gene regulation to exert these functions. We have parted from the initial observation that loss of total macroH2A1 led to a change in the morphology of murine myotubes differentiated ex vivo. The fusion of myoblasts to myotubes is a key process in embryonic myogenesis and highly relevant for muscle regeneration after acute or chronic injury. We have focused on this physiological process, to investigate the functions of the two splice isoforms of macroH2A1. Individual perturbation of the two isoforms in myotubes forming in vitro from myogenic C2C12 cells showed an opposing phenotype, with macroH2A1.1 enhancing, and macroH2A1.2 reducing, fusion. Differential regulation of a subset of fusion-related genes encoding components of the extracellular matrix and cell surface receptors for adhesion correlated with these phenotypes. We describe, for the first time, splice isoform-specific phenotypes for the histone variant macroH2A1 in a physiologic process and provide evidence for a novel underlying molecular mechanism of gene regulation.
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Dates et versions

hal-03052706 , version 1 (10-12-2020)

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Sarah Hurtado-Bagès, Melanija Posavec Marjanovic, Vanesa Valero, Roberto Malinverni, David Corujo, et al.. The Histone Variant MacroH2A1 Regulates Key Genes for Myogenic Cell Fusion in a Splice-Isoform Dependent Manner. Cells, 2020, 9 (5), pp.1109. ⟨10.3390/cells9051109⟩. ⟨hal-03052706⟩
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