ArticleNucleic acids research2016
Differential contribution of cis-regulatory elements to higher order chromatin structure and expression of the CFTR locus.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 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
- Long non-coding RNAs in the CFTR locus: New transcriptional regulators of CFTR gene expression.Molecular therapy. Nucleic acids · 2026Article
- Cholinergic signaling modulates intestinal pathophysiology in a Drosophila model of cystic fibrosis.PLoS genetics · 2026Article
- Novel Cystic Fibrosis Ferret Model Enables Visualization of CFTR Expression Cells and Genetic CFTR Reactivation.Human gene therapy · 2025Article
- 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
- 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
- Three-dimensional genome structure and function.MedComm · 2023Review
- Tissue-Specific Regulation ofInternational journal of molecular sciences · 2023Review
- Article
- Cellular heterogeneity in the 16HBE14oPhysiological reports · 2023Article
- Organoid Technology and Its Role for Theratyping Applications in Cystic Fibrosis.Children (Basel, Switzerland) · 2022Review
- Molecular mechanisms of cystic fibrosis - how mutations lead to misfunction and guide therapy.Bioscience reports · 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
- Epigenome editing of the CFTR-locus for treatment of cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2022Article
- WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas.Human molecular genetics · 2021Article
- Human Molecular Genetics and the long road to treating cystic fibrosis.Human molecular genetics · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Higher order chromatin structure establishes domains that organize the genome and coordinate gene expression. However, the molecular mechanisms controlling transcription of individual loci within a topological domain (TAD) are not fully understood. The cystic fibrosis transmembrane conductance regulator (CFTR) gene provides a paradigm for investigating these mechanisms.CFTR occupies a TAD bordered by CTCF/cohesin binding sites within which are cell-type-selective cis-regulatory elements for the locus. We showed previously that intronic and extragenic enhancers, when occupied by specific transcription factors, are recruited to the CFTR promoter by a looping mechanism to drive gene expression. Here we use a combination of CRISPR/Cas9 editing of cis-regulatory elements and siRNA-mediated depletion of architectural proteins to determine the relative contribution of structural elements and enhancers to the higher order structure and expression of the CFTR locus. We found the boundaries of the CFTRTAD are conserved among diverse cell types and are dependent on CTCF and cohesin complex. Removal of an upstream CTCF-binding insulator alters the interaction profile, but has little effect on CFTR expression. Within the TAD, intronic enhancers recruit cell-type selective transcription factors and deletion of a pivotal enhancer element dramatically decreases CFTR expression, but has minor effect on its 3D structure.
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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.