ArticleAmerican journal of respiratory cell and molecular biology2010
Multiple mechanisms influence regulation of the cystic fibrosis transmembrane conductance regulator gene promoter.
Article in American journal of respiratory cell and molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Epigenetic regulation and chromatin organization in cystic fibrosis airways.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026Review
- Long non-coding RNAs in the CFTR locus: New transcriptional regulators of CFTR gene expression.Molecular therapy. Nucleic acids · 2026Article
- Targeted Therapy for Restoring CFTR Activity: From Experimental to Clinical Features.International journal of molecular sciences · 2026Review
- CFTR Gene Regulation in Human Pancreatic Duct, Bile Duct and Sweat Gland Epithelial Cells.Journal of cellular and molecular medicine · 2025Article
- A promoter-dependent upstream activator augments CFTR expression in diverse epithelial cell types.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Article
- Article
- Identification of cystic fibrosis transmembrane conductance regulator as a prognostic marker for juvenile myelomonocytic leukemia via the whole-genome bisulfite sequencing of monozygotic twins and data mining.Translational pediatrics · 2022Article
- Screening for Regulatory Variants in 460 kb Encompassing the CFTR Locus in Cystic Fibrosis Patients.The Journal of molecular diagnostics : JMD · 2019Article
- Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions.International journal of molecular sciences · 2016Article
- Review
- CHD6 regulates the topological arrangement of the CFTR locus.Human molecular genetics · 2015Article
- Post-transcriptional regulation of cystic fibrosis transmembrane conductance regulator expression and function by microRNAs.American journal of respiratory cell and molecular biology · 2013Article
- The cystic fibrosis gene: a molecular genetic perspective.Cold Spring Harbor perspectives in medicine · 2013Review
- A microRNA network regulates expression and biosynthesis of wild-type and DeltaF508 mutant cystic fibrosis transmembrane conductance regulator.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Nucleosome occupancy reveals regulatory elements of the CFTR promoter.Nucleic acids research · 2012Article
- Deletion of CFTR translation start site reveals functional isoforms of the protein in CF patients.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2009Article
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Authors and funding
6 authors at 2 institutions in 3 countries.
Funding
Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) gene is driven by a promoter that cannot alone account for the temporal and tissue-specific regulation of the gene. This has led to the search for additional regulatory elements that cooperate with the basal promoter to achieve coordinated expression. We previously identified two alternative upstream exons of the gene that were mutually exclusive of the first exon, and one of which showed temporal regulation in the human and sheep lung. We now demonstrate that this alternative splice product generates a stable protein, which initiates translation at an ATG in exon 4, and thus lacks the N terminus of CFTR. The other splice variant inhibits translation of the protein. In a search for the promoter used by the upstream exons, we identified a novel element that contributes to the activity of the basal CFTR promoter in airway epithelial cells, but does not function independently. Finally, we demonstrate that, in primary airway cells, skin fibroblasts, and both airway and intestinal cell lines, the CFTR promoter is unmethylated, irrespective of CFTR expression status. Thus, methylation is not the main cause of inactivation of CFTR transcription.
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Registered trials
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