دورية أكاديمية
Pathomechanisms and biomarkers in facioscapulohumeral muscular dystrophy: roles of DUX4 and PAX7
| العنوان: | Pathomechanisms and biomarkers in facioscapulohumeral muscular dystrophy: roles of DUX4 and PAX7 |
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| المؤلفون: | Christopher R S Banerji, Peter S Zammit |
| المصدر: | EMBO Molecular Medicine, Vol 13, Iss 8, Pp n/a-n/a (2021) |
| بيانات النشر: | Springer Nature, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | biomarker, DUX4, facioscapulohumeral muscular dystrophy (FSHD), pathology, PAX7, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract Facioscapulohumeral muscular dystrophy (FSHD) is characterised by progressive skeletal muscle weakness and wasting. FSHD is linked to epigenetic derepression of the subtelomeric D4Z4 macrosatellite at chromosome 4q35. Epigenetic derepression permits the distal‐most D4Z4 unit to transcribe DUX4, with transcripts stabilised by splicing to a poly(A) signal on permissive 4qA haplotypes. The pioneer transcription factor DUX4 activates target genes that are proposed to drive FSHD pathology. While this toxic gain‐of‐function model is a satisfying “bottom‐up” genotype‐to‐phenotype link, DUX4 is rarely detectable in muscle and DUX4 target gene expression is inconsistent in patients. A reliable biomarker for FSHD is suppression of a target gene score of PAX7, a master regulator of myogenesis. However, it is unclear how this “top‐down” finding links to genomic changes that characterise FSHD and to DUX4. Here, we explore the roles and interactions of DUX4 and PAX7 in FSHD pathology and how the relationship between these two transcription factors deepens understanding via the immune system and muscle regeneration. Considering how FSHD pathomechanisms are represented by “DUX4opathy” models has implications for developing therapies and current clinical trials. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| العلاقة: | https://doaj.org/toc/1757-4676Test; https://doaj.org/toc/1757-4684Test |
| DOI: | 10.15252/emmm.202013695 |
| الوصول الحر: | https://doaj.org/article/c5e23813bf1949a6b6aa84f1244f2a2aTest |
| رقم الانضمام: | edsdoj.5e23813bf1949a6b6aa84f1244f2a2a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 17574676 |
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| DOI: | 10.15252/emmm.202013695 |