ArticleNucleic acids research2020
Looping of upstream cis-regulatory elements is required for CFTR expression in human airway epithelial cells.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Pooled it
- Epigenetic regulation and chromatin organization in cystic fibrosis airways.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026Review
- CFTR activity in nasal potential difference of adults with idiopathic bronchiectasis.Respiratory research · 2026Article
- Distinct regulatory elements of SLC6A14 expression contribute to modification of cystic fibrosis phenotypes.Human genetics · 2026Article
- CFTR Gene Regulation in Human Pancreatic Duct, Bile Duct and Sweat Gland Epithelial Cells.Journal of cellular and molecular medicine · 2025Article
- Novel Cystic Fibrosis Ferret Model Enables Visualization of CFTR Expression Cells and Genetic CFTR Reactivation.Human gene therapy · 2025Article
- Pathogenic germline variants in Chinese pancreatic adenocarcinoma patients.Nature communications · 2025Article
- CatLearning: highly accurate gene expression prediction from histone mark.Briefings in bioinformatics · 2024Article
- 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
- Article
- Chromosomal positioning and epigenetic architecture influence DNA methylation patterns triggered by galactic cosmic radiation.Scientific reports · 2024Article
- Tissue-Specific Regulation ofInternational journal of molecular sciences · 2023Review
- Cellular heterogeneity in the 16HBE14oPhysiological reports · 2023Article
- Article
- Single-Cell RNA Sequencing Reveals New Basic and Translational Insights in the Cystic Fibrosis Lung.American journal of respiratory cell and molecular biology · 2023Review
- Active enhancers strengthen insulation by RNA-mediated CTCF binding at chromatin domain boundaries.Genome research · 2023Article
- Article
- Krüppel-Like Factor 5 Regulates CFTR Expression Through Repression by Maintaining Chromatin Architecture Coupled with Direct Enhancer Activation.Journal of molecular biology · 2022Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The CFTR gene lies within an invariant topologically associated domain (TAD) demarcated by CTCF and cohesin, but shows cell-type specific control mechanisms utilizing different cis-regulatory elements (CRE) within the TAD. Within the respiratory epithelium, more than one cell type expresses CFTR and the molecular mechanisms controlling its transcription are likely divergent between them. Here, we determine how two extragenic CREs that are prominent in epithelial cells in the lung, regulate expression of the gene. We showed earlier that these CREs, located at -44 and -35 kb upstream of the promoter, have strong cell-type-selective enhancer function. They are also responsive to inflammatory mediators and to oxidative stress, consistent with a key role in CF lung disease. Here, we use CRISPR/Cas9 technology to remove these CREs from the endogenous locus in human bronchial epithelial cells. Loss of either site extinguished CFTR expression and abolished long-range interactions between these sites and the gene promoter, suggesting non-redundant enhancers. The deletions also greatly reduced promoter interactions with the 5' TAD boundary. We show substantial recruitment of RNAPII to the -35 kb element and identify CEBPβ as a key activator of airway expression of CFTR, likely through occupancy at this CRE and the gene promoter.
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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.