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Open AccessArticle

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

1
Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-GTP-UAB, 08916 Badalona, Spain
2
Program for Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), 08916 Badalona, Spain
3
Université de Lyon, Ecole Normale Supérieure de Lyon, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon, INSERM 1052, CNRS 5286, F-69008 Lyon, France
4
Center for Integrative Biology (CBI), LBME, University of Toulouse, UPS, CNRS, F-31062 Toulouse, France
*
Author to whom correspondence should be addressed.
Cells 2020, 9(5), 1109; https://doi.org/10.3390/cells9051109
Received: 31 March 2020 / Revised: 21 April 2020 / Accepted: 23 April 2020 / Published: 30 April 2020
(This article belongs to the Special Issue Histone Variants from Structure to Molecular Function)
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. View Full-Text
Keywords: histone variants; myogenic differentiation; myotubes; cell fusion; macroH2A; PARP1; gene regulation; ADP ribose histone variants; myogenic differentiation; myotubes; cell fusion; macroH2A; PARP1; gene regulation; ADP ribose
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MDPI and ACS Style

Hurtado-Bagès, S.; Posavec Marjanovic, M.; Valero, V.; Malinverni, R.; Corujo, D.; Bouvet, P.; Lavigne, A.-C.; Bystricky, K.; Buschbeck, M. The Histone Variant MacroH2A1 Regulates Key Genes for Myogenic Cell Fusion in a Splice-Isoform Dependent Manner. Cells 2020, 9, 1109. https://doi.org/10.3390/cells9051109

AMA Style

Hurtado-Bagès S, Posavec Marjanovic M, Valero V, Malinverni R, Corujo D, Bouvet P, Lavigne A-C, Bystricky K, Buschbeck M. The Histone Variant MacroH2A1 Regulates Key Genes for Myogenic Cell Fusion in a Splice-Isoform Dependent Manner. Cells. 2020; 9(5):1109. https://doi.org/10.3390/cells9051109

Chicago/Turabian Style

Hurtado-Bagès, Sarah; Posavec Marjanovic, Melanija; Valero, Vanesa; Malinverni, Roberto; Corujo, David; Bouvet, Philippe; Lavigne, Anne-Claire; Bystricky, Kerstin; Buschbeck, Marcus. 2020. "The Histone Variant MacroH2A1 Regulates Key Genes for Myogenic Cell Fusion in a Splice-Isoform Dependent Manner" Cells 9, no. 5: 1109. https://doi.org/10.3390/cells9051109

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