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PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle

Banerji, CRS; Panamarova, M; Hebaishi, H; White, RB; Relaix, F; Severini, S; Zammit, PS; (2017) PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle. Nature Communications , 8 , Article 2152. 10.1038/s41467-017-01200-4. Green open access

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Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to hypomethylation of D4Z4 repeats on chromosome 4q causing expression of the DUX4 transcription factor. However, DUX4 is difficult to detect in FSHD muscle biopsies and it is debatable how robust changes in DUX4 target gene expression are as an FSHD biomarker. PAX7 is a master regulator of myogenesis that rescues DUX4-mediated apoptosis. Here, we show that suppression of PAX7 target genes is a hallmark of FSHD, and that it is as major a signature of FSHD muscle as DUX4 target gene expression. This is shown using meta-analysis of over six FSHD muscle biopsy gene expression studies, and validated by RNA-sequencing on FSHD patient-derived myoblasts. DUX4 also inhibits PAX7 from activating its transcriptional target genes and vice versa. Furthermore, PAX7 target gene repression can explain oxidative stress sensitivity and epigenetic changes in FSHD. Thus, PAX7 target gene repression is a hallmark of FSHD that should be considered in the investigation of FSHD pathology and therapy.

Type: Article
Title: PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41467-017-01200-4
Publisher version: http://doi.org/10.1038/s41467-017-01200-4
Language: English
Additional information: Copyright © The Author(s) 2017 Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: https://discovery.ucl.ac.uk/id/eprint/10065038
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