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Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy
Facioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is caused either by the contraction of the D4Z4 macrosatellite repeat at the distal end of chromosome 4q to a size of 1 to 10 repeat units (FSHD1) or by mutations in D4Z4 chromatin modifiers such as Structural Maintenance o...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318180/ https://www.ncbi.nlm.nih.gov/pubmed/32086799 http://dx.doi.org/10.1111/cge.13726 |
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author | Greco, Anna Goossens, Remko van Engelen, Baziel van der Maarel, Silvère M. |
author_facet | Greco, Anna Goossens, Remko van Engelen, Baziel van der Maarel, Silvère M. |
author_sort | Greco, Anna |
collection | PubMed |
description | Facioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is caused either by the contraction of the D4Z4 macrosatellite repeat at the distal end of chromosome 4q to a size of 1 to 10 repeat units (FSHD1) or by mutations in D4Z4 chromatin modifiers such as Structural Maintenance of Chromosomes Hinge Domain Containing 1 (FSHD2). These two genotypes share a phenotype characterized by progressive and often asymmetric muscle weakening and atrophy, and common epigenetic alterations of the D4Z4 repeat. All together, these epigenetic changes converge the two genetic forms into one disease and explain the derepression of the DUX4 gene, which is otherwise kept epigenetically silent in skeletal muscle. DUX4 is consistently transcriptionally upregulated in FSHD1 and FSHD2 skeletal muscle cells where it is believed to exercise a toxic effect. Here we provide a review of the recent literature describing the progress in understanding the complex genetic and epigenetic architecture of FSHD, with a focus on one of the consequences that these epigenetic changes inflict, the DUX4‐induced immune deregulation cascade. Moreover, we review the latest therapeutic strategies, with particular attention to the potential of epigenetic correction of the FSHD locus. |
format | Online Article Text |
id | pubmed-7318180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-73181802020-06-29 Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy Greco, Anna Goossens, Remko van Engelen, Baziel van der Maarel, Silvère M. Clin Genet Invited Reviews Facioscapulohumeral muscular dystrophy (FSHD), a common hereditary myopathy, is caused either by the contraction of the D4Z4 macrosatellite repeat at the distal end of chromosome 4q to a size of 1 to 10 repeat units (FSHD1) or by mutations in D4Z4 chromatin modifiers such as Structural Maintenance of Chromosomes Hinge Domain Containing 1 (FSHD2). These two genotypes share a phenotype characterized by progressive and often asymmetric muscle weakening and atrophy, and common epigenetic alterations of the D4Z4 repeat. All together, these epigenetic changes converge the two genetic forms into one disease and explain the derepression of the DUX4 gene, which is otherwise kept epigenetically silent in skeletal muscle. DUX4 is consistently transcriptionally upregulated in FSHD1 and FSHD2 skeletal muscle cells where it is believed to exercise a toxic effect. Here we provide a review of the recent literature describing the progress in understanding the complex genetic and epigenetic architecture of FSHD, with a focus on one of the consequences that these epigenetic changes inflict, the DUX4‐induced immune deregulation cascade. Moreover, we review the latest therapeutic strategies, with particular attention to the potential of epigenetic correction of the FSHD locus. Blackwell Publishing Ltd 2020-03-04 2020-06 /pmc/articles/PMC7318180/ /pubmed/32086799 http://dx.doi.org/10.1111/cge.13726 Text en © 2020 The Authors. Clinical Genetics published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Invited Reviews Greco, Anna Goossens, Remko van Engelen, Baziel van der Maarel, Silvère M. Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy |
title | Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy |
title_full | Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy |
title_fullStr | Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy |
title_full_unstemmed | Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy |
title_short | Consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy |
title_sort | consequences of epigenetic derepression in facioscapulohumeral muscular dystrophy |
topic | Invited Reviews |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318180/ https://www.ncbi.nlm.nih.gov/pubmed/32086799 http://dx.doi.org/10.1111/cge.13726 |
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