ArticleProceedings of the National Academy of Sciences of the United States of America1999
Induction of utrophin gene expression by heregulin in skeletal muscle cells: role of the N-box motif and GA binding protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 124 citations in OpenAlex.
- CRISPR-Cas9-mediated upregulation of utrophin ameliorates Duchenne muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Single-nuclei sequencing of skeletal muscle reveals subsynaptic-specific transcripts involved in neuromuscular junction maintenance.Nature communications · 2025Article
- L-Arginine Activates the Neuregulin-1/ErbB Receptor Signaling Pathway and Increases Utrophin mRNA Levels in C2C12 Cells.Biochemistry research international · 2025Article
- Utrophin modulator drugs as potential therapies for Duchenne and Becker muscular dystrophies.Neuropathology and applied neurobiology · 2021Article
- Targeting IRES-dependent translation as a novel approach for treating Duchenne muscular dystrophy.RNA biology · 2021Review
- Identification of therapeutics that target eEF1A2 and upregulate utrophin A translation in dystrophic muscles.Nature communications · 2020Article
- High-throughput identification of post-transcriptional utrophin up-regulators for Duchenne muscle dystrophy (DMD) therapy.Scientific reports · 2020Article
- Chemical Proteomics and Phenotypic Profiling Identifies the Aryl Hydrocarbon Receptor as a Molecular Target of the Utrophin Modulator Ezutromid.Angewandte Chemie (International ed. in English) · 2020Article
- The Neuromuscular Junction in Health and Disease: Molecular Mechanisms Governing Synaptic Formation and Homeostasis.Frontiers in molecular neuroscience · 2020Review
- Do porcine Sertoli cells represent an opportunity for Duchenne muscular dystrophy?Cell proliferation · 2019Review
- High throughput screening in duchenne muscular dystrophy: from drug discovery to functional genomics.Biology · 2014Review
- Translational regulation of utrophin by miRNAs.PloS one · 2011Article
- Targeting artificial transcription factors to the utrophin A promoter: effects on dystrophic pathology and muscle function.The Journal of biological chemistry · 2008Article
- Modulation of utrophin A mRNA stability in fast versus slow muscles via an AU-rich element and calcineurin signaling.Nucleic acids research · 2008Article
- Heregulin-induced epigenetic regulation of the utrophin-A promoter.FEBS letters · 2007Article
- Ets-2 repressor factor silences extrasynaptic utrophin by N-box mediated repression in skeletal muscle.Molecular biology of the cell · 2007Article
- Staufen1 regulates diverse classes of mammalian transcripts.The EMBO journal · 2007Article
- Postsynaptic chromatin is under neural control at the neuromuscular junction.The EMBO journal · 2007Article
- Neuromuscular synapse formation in mice lacking motor neuron- and skeletal muscle-derived Neuregulin-1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2006Article
- Identification of a crucial site for synoviolin expression.Molecular and cellular biology · 2005Article
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The modulation of utrophin gene expression in muscle by the nerve-derived factor agrin plausibly involves the trophic factor ARIA/heregulin. Here we show that heregulin treatment of mouse and human cultured myotubes caused a approximately 2.5-fold increase in utrophin mRNA levels. Transient transfection experiments with utrophin promoter-reporter gene constructs showed that this increase resulted from an enhanced transcription of the utrophin gene. In the case of the nicotinic acetylcholine receptor delta and epsilon subunit genes, heregulin was previously reported to stimulate transcription via a conserved promoter element, the N-box, which binds the multimeric Ets-related transcription factor GA binding protein (GABP). Accordingly, site-directed mutagenesis of a single N-box motif in the utrophin gene promoter abolished the transcriptional response to heregulin. In addition, overexpression of heregulin, or of the two GABP subunits in cultured myotubes, caused an N-box-dependent increase of the utrophin promoter activity. In vivo, direct gene transfer into muscle confirmed that heregulin regulates utrophin gene expression. Finally, electrophoretic mobility shift assays and supershift experiments performed with muscle extracts revealed that the N-box of the utrophin promoter binds GABP. These findings suggest that the subsynaptic activation of transcription by heregulin via the N-box motif and GABP are conserved among genes expressed at the neuromuscular junction. Because utrophin can functionally compensate for the lack of dystrophin, the elucidation of the molecular mechanisms regulating utrophin gene transcription may ultimately lead to therapies based on utrophin expression throughout the muscle fibers of Duchenne muscular dystrophy patients.
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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.