ArticleEpigenetics2015
Increased DUX4 expression during muscle differentiation correlates with decreased SMCHD1 protein levels at D4Z4.
Article in Epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 69 citations in OpenAlex.
- Nanopore Ultra-Long Sequencing for FSHD: From Molecular Diagnosis to Preimplantation Genetic Testing.Genes · 2026Review
- SMCHD1 Is Dispensable for Repeat-Induced FMR1 Hypermethylation in Fragile X Pluripotent Stem Cells.International journal of molecular sciences · 2026Article
- Impaired Myogenic Differentiation Is a Shared Feature Across Genetic Myopathies.International journal of molecular sciences · 2026Review
- Elevated labile iron contributes to membrane repair deficits in facioscapulohumeral muscular dystrophy.iScience · 2026Article
- Rethinking genomics of facioscapulohumeral muscular dystrophy in the telomere-to-telomere era: pitfalls in the hidden landscape of D4Z4 repeats.European journal of human genetics : EJHG · 2026Article
- All-in-one vectors for epigenetic CRISPR inhibition ofMolecular therapy. Methods & clinical development · 2025Article
- A discrete region of the D4Z4 is sufficient to initiate epigenetic silencing.Human molecular genetics · 2025Article
- DUX4 at 25: how it emerged from "junk DNA" to become the cause of facioscapulohumeral muscular dystrophy.Skeletal muscle · 2025Review
- Three-dimensional tissue engineered skeletal muscle modelling facioscapulohumeral muscular dystrophy.Brain : a journal of neurology · 2025Article
- Facioscapulohumeral Dystrophy: Molecular Basis and Therapeutic Opportunities.Cold Spring Harbor perspectives in biology · 2025Review
- The Unexplored Role of Connexin Hemichannels in Promoting Facioscapulohumeral Muscular Dystrophy Progression.International journal of molecular sciences · 2025Review
- SIX transcription factors are necessary for the activation of DUX4 expression in facioscapulohumeral muscular dystrophy.Skeletal muscle · 2024Article
- snRNA-seq analysis in multinucleated myogenic FSHD cells identifies heterogeneous FSHD transcriptome signatures associated with embryonic-like program activation and oxidative stress-induced apoptosis.Human molecular genetics · 2024Article
- SMCHD1 has separable roles in chromatin architecture and gene silencing that could be targeted in disease.Nature communications · 2023Article
- SMCHD1 and LRIF1 converge at the FSHD-associated D4Z4 repeat and LRIF1 promoter yet display different modes of action.Communications biology · 2023Article
- WDR5 is required for DUX4 expression and its pathological effects in FSHD muscular dystrophy.Nucleic acids research · 2023Article
- Influence ofInternational journal of molecular sciences · 2023Review
- Facioscapulohumeral muscular dystrophy: the road to targeted therapies.Nature reviews. Neurology · 2023Review
- A Targeted Approach for Evaluating DUX4-Regulated Proteins as Potential Serum Biomarkers for Facioscapulohumeral Muscular Dystrophy Using Immunoassay Proteomics.Journal of neuromuscular diseases · 2023Article
- FSHD Therapeutic Strategies: What Will It Take to Get to Clinic?Journal of personalized medicine · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Facioscapulohumeral muscular dystrophy is caused by incomplete epigenetic repression of the transcription factor DUX4 in skeletal muscle. A copy of DUX4 is located within each unit of the D4Z4 macrosatellite repeat array and its derepression in somatic cells is caused by either repeat array contraction (FSHD1) or by mutations in the chromatin repressor SMCHD1 (FSHD2). While DUX4 expression has thus far only been detected in FSHD muscle and muscle cell cultures, and increases with in vitro myogenic differentiation, the D4Z4 chromatin structure has only been studied in proliferating myoblasts or non-myogenic cells. We here show that SMCHD1 protein levels at D4Z4 decline during muscle cell differentiation and correlate with DUX4 derepression. In FSHD2, but not FSHD1, the loss of SMCHD1 repressor activity is partially compensated by increased Polycomb Repressive Complex 2 (PRC2)-mediated H3K27 trimethylation at D4Z4, a situation that can be mimicked by SMCHD1 knockdown in control myotubes. In contrast, moderate overexpression of SMCHD1 results in DUX4 silencing in FSHD1 and FSHD2 myotubes demonstrating that DUX4 derepression in FSHD is reversible. Together, we show that in FSHD1 and FSHD2 the decline in SMCHD1 protein levels during muscle cell differentiation renders skeletal muscle sensitive to DUX4.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.