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Estrogens enhance myoblast differentiation in facioscapulohumeral muscular dystrophy by antagonizing DUX4 activity

Lookup NU author(s): Professor Giorgio TascaORCiD


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Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder that is characterized by extreme variability in symptoms, with females being less severely affected than males and presenting a higher proportion of asymptomatic carriers. The sex-related factors involved in the disease are not known. Here, we have utilized myoblasts isolated from FSHD patients (FSHD myoblasts) to investigate the effect of estrogens on muscle properties. Our results demonstrated that estrogens counteract the differentiation impairment of FSHD myoblasts without affecting cell proliferation or survival. Estrogen effects are mediated by estrogen receptor ? (ER?), which reduces chromatin occupancy and transcriptional activity of double homeobox 4 (DUX4), a protein whose aberrant expression has been implicated in FSHD pathogenesis. During myoblast differentiation, we observed that the levels and activity of DUX4 increased progressively and were associated with its enhanced recruitment in the nucleus. ER? interfered with this recruitment by relocalizing DUX4 in the cytoplasm. This work identifies estrogens as a potential disease modifier that underlie sex-related differences in FSHD by protecting against myoblast differentiation impairments in this disease.

Publication metadata

Author(s): Teveroni E, Pellegrino M, Sacconi S, Calandra P, Cascino I, Farioli-Vecchioli S, Puma A, Garibaldi M, Morosetti R, Tasca G, Ricci E, Trevisan CP, Galluzzi G, Pontecorvi A, Crescenzi M, Deidda G, Moretti F

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Investigation

Year: 2017

Volume: 127

Issue: 4

Pages: 1531-1545

Print publication date: 03/04/2017

Online publication date: 03/03/2017

Acceptance date: 12/01/2017

ISSN (print): 0021-9738

ISSN (electronic): 1558-8238

Publisher: American Society for Clinical Investigation


DOI: 10.1172/JCI89401

PubMed id: 28263188


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