ArticleProceedings of the National Academy of Sciences of the United States of America2009
Intronic enhancers coordinate epithelial-specific looping of the active CFTR locus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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
77 citing papers in PubMed, 111 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
- CFTR Gene Regulation in Human Pancreatic Duct, Bile Duct and Sweat Gland Epithelial Cells.Journal of cellular and molecular medicine · 2025Article
- Article
- A promoter-dependent upstream activator augments CFTR expression in diverse epithelial cell types.Biochimica et biophysica acta. Gene regulatory mechanisms · 2024Article
- Investigating adverse genomic and regulatory changes caused by replacement of the full-lengthMolecular therapy. Nucleic acids · 2024Article
- The impact of genomic distance on enhancer-promoter interactions at the CFTR locus.Journal of cellular and molecular medicine · 2024Article
- An injury-responsiveScience advances · 2023Article
- Tissue-Specific Regulation ofInternational journal of molecular sciences · 2023Review
- Article
- Cellular heterogeneity in the 16HBE14oPhysiological reports · 2023Article
- Molecular mechanisms of cystic fibrosis - how mutations lead to misfunction and guide therapy.Bioscience reports · 2022Review
- A novel role for CFTR interaction with LH and FGF in azoospermia and epididymal maldevelopment caused by cryptorchidism.Basic and clinical andrology · 2022Review
- Krüppel-Like Factor 5 Regulates CFTR Expression Through Repression by Maintaining Chromatin Architecture Coupled with Direct Enhancer Activation.Journal of molecular biology · 2022Article
- Article
- Targeted replacement of full-length CFTR in human airway stem cells by CRISPR-Cas9 for pan-mutation correction in the endogenous locus.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Epigenome editing of the CFTR-locus for treatment of cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2022Article
- Enhancers with tissue-specific activity are enriched in intronic regions.Genome research · 2021Article
- OTX2 regulates CFTR expression during endoderm differentiation and occupies 3' cis-regulatory elements.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Article
- Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
The regulated expression of large human genes can depend on long-range interactions to establish appropriate three-dimensional structures across the locus. The cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encompasses 189 kb of genomic DNA, shows a complex pattern of expression with both spatial and temporal regulation. The flanking loci, ASZ1 and CTTNBP2, show very different tissue-specific expression. The mechanisms governing control of CFTR expression remain poorly understood, although they are known to involve intronic regulatory elements. Here, we show a complex looped structure of the CFTR locus in cells that express the gene, which is absent from cells in which the gene is inactive. By using chromatin conformation capture (3C) with a bait probe at the CFTR promoter, we demonstrate close interaction of this region with sequences in the middle of the gene about 100 kb from the promoter and with regions 3' to the locus that are about 200 kb away. We show that these interacting regions correspond to prominent DNase I hypersensitive sites within the locus. Moreover, these sequences act cooperatively in reporter gene constructs and recruit proteins that modify chromatin structure. The model for CFTR gene expression that is revealed by our data provides a paradigm for other large genes with multiple regulatory elements lying within both introns and intergenic regions. We anticipate that these observations will enable original approaches to designing regulated transgenes for tissue-specific gene therapy protocols.
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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.