The Histone Variant MacroH2A1 Regulates Key Genes for Myogenic Cell Fusion in a Splice-Isoform Dependent Manner.
Por:
Hurtado-Bagès S, Posavec Marjanovic M, Valero V, Malinverni R, Corujo D, Bouvet P, Lavigne AC, Bystricky K and Buschbeck M
Publicada:
30 abr 2020
Ahead of Print:
30 abr 2020
Resumen:
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.
Filiaciones:
:
Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-GTP-UAB, 08916 Badalona, Spain
Posavec Marjanovic M:
Program for Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), 08916 Badalona, Spain
:
Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-GTP-UAB, 08916 Badalona, Spain
Malinverni R:
Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-GTP-UAB, 08916 Badalona, Spain
:
Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-GTP-UAB, 08916 Badalona, Spain
Bouvet P:
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
Lavigne AC:
Center for Integrative Biology (CBI), LBME, University of Toulouse, UPS, CNRS, F-31062 Toulouse, France
Bystricky K:
Center for Integrative Biology (CBI), LBME, University of Toulouse, UPS, CNRS, F-31062 Toulouse, France
:
Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-GTP-UAB, 08916 Badalona, Spain
Program for Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), 08916 Badalona, Spain
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