ArticleSkeletal muscle2016
DNA-binding sequence specificity of DUX4.
Article in Skeletal muscle, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- p53-independent DUX4 pathology in cell and animal models of facioscapulohumeral muscular dystrophy.Disease models & mechanisms · 2017Pooled it
- DUX4 at 25: how it emerged from "junk DNA" to become the cause of facioscapulohumeral muscular dystrophy.Skeletal muscle · 2025Review
- DUX4-r exerts a neomorphic activity that depends on GTF2I in acute lymphoblastic leukemia.Science advances · 2023Article
- Review
- Analysis of genes regulated by DUX4 via oxidative stress reveals potential therapeutic targets for treatment of facioscapulohumeral dystrophy.Redox biology · 2021Article
- Facioscapulohumeral muscular dystrophy: genetics, gene activation and downstream signalling with regard to recent therapeutic approaches: an update.Orphanet journal of rare diseases · 2021Review
- A Deoxyribonucleic Acid Decoy Trapping DUX4 for the Treatment of Facioscapulohumeral Muscular Dystrophy.Molecular therapy. Nucleic acids · 2020Article
- Cellular and animal models for facioscapulohumeral muscular dystrophy.Disease models & mechanisms · 2020Review
- Transcriptional and cytopathological hallmarks of FSHD in chronic DUX4-expressing mice.The Journal of clinical investigation · 2020Article
- DNA aptamers against the DUX4 protein reveal novel therapeutic implications for FSHD.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Crystal Structure of the Double Homeodomain of DUX4 in Complex with DNA.Cell reports · 2018Article
- Disentangling transcription factor binding site complexity.Nucleic acids research · 2018Article
- Low level DUX4 expression disrupts myogenesis through deregulation of myogenic gene expression.Scientific reports · 2018Article
- Article
- Functional domains of the FSHD-associated DUX4 protein.Biology open · 2018Article
- Overexpression of the double homeodomain protein DUX4c interferes with myofibrillogenesis and induces clustering of myonuclei.Skeletal muscle · 2018Article
- PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle.Nature communications · 2017Article
- The DUX4 homeodomains mediate inhibition of myogenesis and are functionally exchangeable with the Pax7 homeodomain.Journal of cell science · 2017Article
- Estrogens enhance myoblast differentiation in facioscapulohumeral muscular dystrophy by antagonizing DUX4 activity.The Journal of clinical investigation · 2017Article
- Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMisexpression of the double homeodomain transcription factor DUX4 results in facioscapulohumeral muscular dystrophy (FSHD). A DNA-binding consensus with two tandem TAAT motifs based on chromatin IP peaks has been discovered; however, the consensus has multiple variations (flavors) of unknown relative activity. In addition, not all peaks have this consensus, and the Pitx1 promoter, the first DUX4 target sequence mooted, has a different TAAT-rich sequence. Furthermore, it is not known whether and to what extent deviations from the consensus affect DNA-binding affinity and transcriptional activation potential.
resultsHere, we take both unbiased and consensus sequence-driven approaches to determine the DNA-binding specificity of DUX4 and its tolerance to mismatches at each site within its consensus sequence. We discover that the best binding and the greatest transcriptional activation are observed when the two TAAT motifs are separated by a C residue. The second TAAT motif in the consensus sequence is actually (T/C)AAT. We find that a T is preferred here. DUX4 has no transcriptional activity on "half-sites", i.e., those bearing only a single TAAT motif. We further find that DUX4 does not bind to the TAATTA motif in the Pitx1 promoter, that Pitx1 sequences have no competitive band shift activity, and that the Pitx1 sequence is transcriptionally inactive, calling into question PITX1 as a DUX4 target gene. Finally, by multimerizing binding sites, we find that DUX4 transcriptional activation demonstrates tremendous synergy and that at low DNA concentrations, at least two motifs are necessary to detect a transcriptional response.
conclusionsThese studies illuminate the DNA-binding sequence preferences of DUX4.
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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.