Evidence map›Paper›PMID 26673704›Full record

ArticleNucleic acids research2016

Differential contribution of cis-regulatory elements to higher order chromatin structure and expression of the CFTR locus.

Rui Yang, Jenny L Kerschner, Nehal Gosalia, Daniel Neems, Lidija K Gorsic, Alexias Safi, Gregory E Crawford, Steven T Kosak, Shih-Hsing Leir, Ann Harris

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.

  1. CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Pooled it
  2. Epigenetic regulation and chromatin organization in cystic fibrosis airways.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Tissue-Specific Regulation ofInternational journal of molecular sciences · 2023
    Review
  12. Article
  13. Cellular heterogeneity in the 16HBE14oPhysiological reports · 2023
    Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Epigenome editing of the CFTR-locus for treatment of cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2022
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Rui YangHuman Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Jenny L KerschnerHuman Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Nehal GosaliaHuman Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Daniel NeemsDepartment of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Lidija K GorsicHuman Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Alexias SafiDivision of Medical Genetics, Department of Pediatrics and Center for Genomic and Computational Biology, Duke University Medical School, Durham, NC 27708, USA.
Gregory E CrawfordDivision of Medical Genetics, Department of Pediatrics and Center for Genomic and Computational Biology, Duke University Medical School, Durham, NC 27708, USA.
Steven T KosakDepartment of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Shih-Hsing LeirHuman Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Ann HarrisHuman Molecular Genetics Program, Lurie Children's Research Center, Chicago, IL 60614, USA Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA ann-harris@northwestern.edu.
Northwestern University · USDuke University · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
Tissue-specific regulation of a gene essential for normal airway epitheliaR01HL094585 · NHLBI · LURIE CHILDREN'S HOSPITAL OF CHICAGO · PI HARRIS, ANN · 2009 to 2020
$2.9M
Transcriptional Networks Regulating Luminal Environment in the EpididymisR01HD068901 · NICHD · LURIE CHILDREN'S HOSPITAL OF CHICAGO · PI HARRIS, ANN · 2011 to 2023
$2.8M
Self-Organization of the Human GenomeDP2OD008717 · OD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI KOSAK, STEVEN TODD · 2011 to 2016
$2.8M
NCI NIH HHS P30 CA060553NHLBI NIH HHS R01 HL094585NICHD NIH HHS R01 HD068901NICHD NIH HHS R01HD068901NIH HHS DP2OD008717
6 · The paper itself

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.

Indexed as

Enhancer Elements, GeneticGene Expression RegulationInsulator ElementsCaco-2 CellsCCCTC-Binding FactorCell Cycle ProteinsCell LineCells, CulturedChromatinChromosomal Proteins, Non-HistoneCohesinsCystic Fibrosis Transmembrane Conductance RegulatorGenetic LociHumansRepressor ProteinsCCCTC-Binding FactorCell Cycle ProteinsChromatinChromosomal Proteins, Non-HistoneCohesinsCTCF protein, humanCystic Fibrosis Transmembrane Conductance RegulatorRepressor Proteins

Identifiers

PMID26673704
PMCPMC4838340
OpenAlexW2336444833

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.