ArticleHuman molecular genetics2015
Direct interplay between two candidate genes in FSHD muscular dystrophy.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- WDR5 is required for DUX4 expression and its pathological effects in FSHD muscular dystrophy.Nucleic acids research · 2023Article
- Facioscapulohumeral muscular dystrophy: the road to targeted therapies.Nature reviews. Neurology · 2023Review
- Pathomechanisms and biomarkers in facioscapulohumeral muscular dystrophy: roles of DUX4 and PAX7.EMBO molecular medicine · 2021Review
- Genetic Approaches for the Treatment of Facioscapulohumeral Muscular Dystrophy.Frontiers in pharmacology · 2021Review
- Type 1 FSHD with 6-10 Repeated Units: Factors Underlying Severity in Index Cases and Disease Penetrance in Their Relatives Attention.International journal of molecular sciences · 2020Article
- DUX4 Signalling in the Pathogenesis of Facioscapulohumeral Muscular Dystrophy.International journal of molecular sciences · 2020Review
- Current status and future prospect of FSHD region gene 1.Journal of biosciences · 2017Review
- DUX4 induces a transcriptome more characteristic of a less-differentiated cell state and inhibits myogenesis.Journal of cell science · 2016Article
- Segregation between SMCHD1 mutation, D4Z4 hypomethylation and Facio-Scapulo-Humeral Dystrophy: a case report.BMC medical genetics · 2016Article
- Cardiac Meets Skeletal: What's New in Microfluidic Models for Muscle Tissue Engineering.Molecules (Basel, Switzerland) · 2016Review
- Transgenic Drosophila for Investigating DUX4 and FRG1, Two Genes Associated with Facioscapulohumeral Muscular Dystrophy (FSHD).PloS one · 2016Article
- Emerging preclinical animal models for FSHD.Trends in molecular medicine · 2015Review
- FHL1 reduces dystrophy in transgenic mice overexpressing FSHD muscular dystrophy region gene 1 (FRG1).PloS one · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common neuromuscular disorders. The major form of the disease (FSHD1) is linked to decrease in copy number of a 3.3-kb tandem repeated macrosatellite (D4Z4), located on chromosome 4q35. D4Z4 deletion alters chromatin structure of the locus leading to aberrant expression of nearby 4q35 genes. Given the high variability in disease onset and progression, multiple factors could contribute to the pathogenesis of FSHD. Among the FSHD candidate genes are double homeobox 4 (DUX4), encoded by the most telomeric D4Z4 unit, and FSHD region gene 1 (FRG1). DUX4 is a sequence-specific transcription factor. Here, we located putative DUX4 binding sites in the human FRG1 genomic area and we show specific DUX4 association to these regions. We found also that ectopically expressed DUX4 up-regulates the endogenous human FRG1 gene in healthy muscle cells, while DUX4 knockdown leads to a decrease in FRG1 expression in FSHD muscle cells. Moreover, DUX4 binds directly and specifically to its binding site located in the human FRG1 gene and transactivates constructs containing FRG1 genomic regions. Intriguingly, the mouse Frg1 genomic area lacks DUX4 binding sites and DUX4 is unable to activate the endogenous mouse Frg1 gene providing a possible explanation for the lack of muscle phenotype in DUX4 transgenic mice. Altogether, our results demonstrate that FRG1 is a direct DUX4 transcriptional target uncovering a novel regulatory circuit contributing to FSHD.
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