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Sci Rep. 2018 Aug 22;8(1):12629. doi: 10.1038/s41598-018-31102-4.

CBP and P300 regulate distinct gene networks required for human primary myoblast differentiation and muscle integrity.

Author information

1
Centre de Biologie du Développement (CBD), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France.
2
Lillehei Heart Institute, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
3
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), CNRS UMR 7104, INSERM U964, University of Strasbourg, Illkirch, France.
4
Universite Clermont Auvergne, CNRS, Inserm, GReD, F-63000, Clermont-Ferrand I, France.
5
Inserm U1046-UMR CNRS 9214, Physiologie et Médecine Expérimentale du cœur et des muscles PHYMEDEXP, CHU A. De Villeneuve, Bâtiment Crastes de Paulet, 371 avenue du doyen Giraud, F-34295, Montpellier cedex 5, France.
6
Centre de Biologie du Développement (CBD), Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, Toulouse, France. laurence.vandel@uca.fr.
7
Universite Clermont Auvergne, CNRS, Inserm, GReD, F-63000, Clermont-Ferrand I, France. laurence.vandel@uca.fr.

Abstract

The acetyltransferases CBP and P300 have been implicated in myogenesis in mouse immortalized cell lines but these studies focused only on the expression of a handful of myogenic factors. Hence, the respective role of these two related cofactors and their impact at global scale on gene expression rewiring during primary myoblast differentiation remain unknown. Here, we characterised the gene networks regulated by these two epigenetic enzymes during human primary myoblast differentiation (HPM). We found that CBP and p300 play a critical role in the activation of the myogenic program and mostly regulate distinct gene sets to control several aspects of HPM biology, even though they also exhibit some degree of redundancy. Moreover, CBP or P300 knockdown strongly impaired muscle cell adhesion and resulted in the activation of inflammation markers, two hallmarks of dystrophic disease. This was further validated in zebrafish where inhibition of CBP and P300 enzymatic activities led to cell adhesion defects and muscle fiber detachment. Our data highlight an unforeseen link between CBP/P300 activity and the emergence of dystrophic phenotypes. They thereby identify CBP and P300 as mediators of adult muscle integrity and suggest a new lead for intervention in muscular dystrophy.

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