Evidence map›Paper›PMID 24440874›Full record

ArticleEpigenetics2014

Chromatin remodeling mediated by the FOXA1/A2 transcription factors activates CFTR expression in intestinal epithelial cells.

Jenny L Kerschner, Nehal Gosalia, Shih-Hsing Leir, Ann Harris

Open access · bronzeAbstract read
In one paragraph

Article in Epigenetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
2.8field-weighted citation impact, top 9% 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

39 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Tissue-Specific Regulation ofInternational journal of molecular sciences · 2023
    Review
  9. Article
  10. Article
  11. Article
  12. 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
  13. OTX2 regulates CFTR expression during endoderm differentiation and occupies 3' cis-regulatory elements.Developmental dynamics : an official publication of the American Association of Anatomists · 2021
    Article
  14. International journal of molecular sciences · 2021
    Article
  15. Article
  16. The FOXA1 transcriptional network coordinates key functions of primary human airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2020
    Article
  17. Article
  18. Genetic variation in CFTR and modifier loci may modulate cystic fibrosis disease severity.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2020
    Review
  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

4 authors at 1 institution in 1 country.

Jenny L KerschnerHuman Molecular Genetics Program; Lurie Children's Research Center; Chicago, IL USA; Department of Pediatrics; Northwestern University Feinberg School of Medicine; Chicago, IL USA.
Nehal GosaliaHuman Molecular Genetics Program; Lurie Children's Research Center; Chicago, IL USA; Department of Pediatrics; Northwestern University Feinberg School of Medicine; Chicago, IL USA.
Shih-Hsing LeirHuman Molecular Genetics Program; Lurie Children's Research Center; Chicago, IL USA; Department of Pediatrics; Northwestern University Feinberg School of Medicine; Chicago, IL USA.
Ann HarrisHuman Molecular Genetics Program; Lurie Children's Research Center; Chicago, IL USA; Department of Pediatrics; Northwestern University Feinberg School of Medicine; Chicago, IL USA.
Northwestern University · US

Funding

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
NHLBI NIH HHS R01 HL094585NHLBI NIH HHS R01HL094585NICHD NIH HHS R01 HD068901NICHD NIH HHS R01HD68901
6 · The paper itself

Abstract

The forkhead box A transcription factors, FOXA1 and FOXA2, function as pioneer factors to open condensed chromatin and facilitate binding of other proteins. We showed previously that these factors are key components of a transcriptional network that drives enhancer function at the cystic fibrosis transmembrane conductance regulator (CFTR) locus in intestinal epithelial cells. The CFTR promoter apparently lacks tissue-specific regulatory elements and expression of the gene is controlled by multiple cis-acting elements, which coordinate gene expression in different cell types. Here we show that concurrent depletion of FOXA1 and FOXA2 represses CFTR expression and alters the three-dimensional architecture of the active locus by diminishing interactions between the promoter and intronic cis-acting elements. Reduction of FOXA1/A2 also modifies the enrichment profile of the active enhancer marks H3K27ac and H3K4me2 across the CFTR locus and alters chromatin accessibility at individual cis-elements. Moreover, loss of FOXA1/A2 suppresses the recruitment of other members of the transcriptional network including HNF1 and CDX2, to multiple cis-elements. These data reveal a complex molecular mechanism underlying the role of FOXA1/A2 in achieving high levels of CFTR expression in intestinal epithelial cells.

Indexed as

Chromatin Assembly and DisassemblyCell LineCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsHepatocyte Nuclear Factor 3-alphaHepatocyte Nuclear Factor 3-betaHistonesHumansIntestinal MucosaIntronsProtein Processing, Post-TranslationalCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorFOXA1 protein, humanFOXA2 protein, humanHepatocyte Nuclear Factor 3-alphaHepatocyte Nuclear Factor 3-betaHistonesCFTRchromatin remodelingFOXApioneer factortranscriptional network

Identifiers

PMID24440874
PMCPMC4121366
OpenAlexW2028130907

What OpenQuestion holds

Textmetadata
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.