The Trithorax Protein Ash1L Promotes Myoblast Fusion by Activating Cdon Expression

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Nov 30

PMID 30487570

Citations 11

Authors

Ilaria Castiglioni

Roberta Caccia

Jose Manuel Garcia-Manteiga

Giulia Ferri

Giuseppina Caretti

Ivan Molineris

Kenichi Nishioka

Davide Gabellini

Affiliations

Soon will be listed here.

Abstract

Myoblast fusion (MF) is required for muscle growth and repair, and its alteration contributes to muscle diseases. The mechanisms governing this process are incompletely understood, and no epigenetic regulator has been previously described. Ash1L is an epigenetic activator belonging to the Trithorax group of proteins and is involved in FSHD muscular dystrophy, autism and cancer. Its physiological role in skeletal muscle is unknown. Here we report that Ash1L expression is positively correlated with MF and reduced in Duchenne muscular dystrophy. In vivo, ex vivo and in vitro experiments support a selective and evolutionary conserved requirement for Ash1L in MF. RNA- and ChIP-sequencing indicate that Ash1L is required to counteract Polycomb repressive activity to allow activation of selected myogenesis genes, in particular the key MF gene Cdon. Our results promote Ash1L as an important epigenetic regulator of MF and suggest that its activity could be targeted to improve cell therapy for muscle diseases.

Citing Articles

Structure-function relationship of ASH1L and histone H3K36 and H3K4 methylation.

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