The Histone Variant MacroH2A1 Regulates Key Genes for Myogenic Cell Fusion in a Splice-Isoform Dependent Manner
Hurtado-Bagès, Sarah (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Posavec Marjanovic, Melanija (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Valero, Vanesa (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Malinverni, Roberto (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Corujo, David (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Bouvet, Philippe (Centre National de la Recherche Scientifique (França))
Lavigne, A. C. (Center for Integrative Biology (CBI). LBME. University of Toulouse. UPS. CNRS)
Bystricky, K. (Center for Integrative Biology (CBI). LBME. University of Toulouse. UPS. CNRS)
Buschbeck, Marcus (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	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.
Grants:	European Commission 675610 Ministerio de Economía y Competitividad RTI2018-094005-B-I00 Ministerio de Economía y Competitividad BFU2015-66559-P Instituto de Salud Carlos III PIE16-00011 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-305
Note:	Altres ajuts: This research project was supported by the Fundació La Marató de TV3 257/C/2019 (to MB). Research at the IJC is supported by the 'La Caixa' Foundation, the Fundació Internacional Josep Carreras, Celgene Spain.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	ADP ribose ; PARP1 ; Cell fusion ; Gene regulation ; Histone variants ; MacroH2A ; Myogenic differentiation ; Myotubes
Published in:	Cells, Vol. 9 Núm. 5 (30 2020) , ISSN 2073-4409

DOI: 10.3390/cells9051109
PMID: 32365743

17 p, 1.9 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles