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Article Dans Une Revue Nature Communications Année : 2022

A fast Myosin super enhancer dictates muscle fiber phenotype through competitive interactions with Myosin genes

Maud Wurmser
  • Fonction : Auteur
Rémi Pierre
  • Fonction : Auteur
Francina Langa
Alain Schmitt
  • Fonction : Auteur
Iori Sakakibara
  • Fonction : Auteur correspondant
Pascal Maire
  • Fonction : Auteur correspondant

Résumé

The contractile properties of adult myofibers are shaped by their Myosin heavy chain isoform content. Here, we identify by snATAC-seq a 42 kb super-enhancer at the locus regrouping the fast Myosin genes. By 4C-seq we show that active fast Myosin promoters interact with this super-enhancer by DNA looping, leading to the activation of a single promoter per nucleus. A rainbow mouse transgenic model of the locus including the super-enhancer recapitulates the endogenous spatio-temporal expression of adult fast Myosin genes. In situ deletion of the super-enhancer by CRISPR/Cas9 editing demonstrates its major role in the control of associated fast Myosin genes, and deletion of two fast Myosin genes at the locus reveals an active competition of the promoters for the shared super-enhancer. Last, by disrupting the organization of fast Myosin , we uncover positional heterogeneity within limb skeletal muscles that may underlie selective muscle susceptibility to damage in certain myopathies.
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Origine : Publication financée par une institution

Dates et versions

pasteur-03709535 , version 1 (09-11-2021)
pasteur-03709535 , version 2 (29-06-2022)

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Matthieu dos Santos, Stéphanie Backer, Frédéric Auradé, Matthew Man-Kin Wong, Maud Wurmser, et al.. A fast Myosin super enhancer dictates muscle fiber phenotype through competitive interactions with Myosin genes. Nature Communications, 2022, 13 (1), pp.1039. ⟨10.1038/s41467-022-28666-1⟩. ⟨pasteur-03709535v2⟩
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