Evidence map›Paper›PMID 22671145›Full record

ArticleThe Biochemical journal2012

Transcriptional networks driving enhancer function in the CFTR gene.

Jenny L Kerschner, Ann Harris

Abstract read
In one paragraph

Article in The Biochemical journal, 2012. 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
3.7field-weighted citation impact, top 7% 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, 45 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Lower Expression ofCancers · 2023
    Article
  7. Article
  8. Article
  9. 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
  10. Revisiting CFTR Interactions: Old Partners and New Players.International journal of molecular sciences · 2021
    Review
  11. International journal of molecular sciences · 2021
    Article
  12. Article
  13. Ivacaftor Reverses Airway Mucus Abnormalities in a Rat Model Harboring a Humanized G551D-CFTR.American journal of respiratory and critical care medicine · 2020
    Article
  14. The FOXA1 transcriptional network coordinates key functions of primary human airway epithelial cells.American journal of physiology. Lung cellular and molecular physiology · 2020
    Article
  15. 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
  16. Article
  17. Coordinate regulation of ELF5 and EHF at the chr11p13 CF modifier region.Journal of cellular and molecular medicine · 2019
    Article
  18. Review
  19. Review
  20. Article
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

2 authors at 1 institution in 1 country.

Jenny L KerschnerHuman Molecular Genetics Program, Children's Memorial Research Center, Chicago, IL 60614, USA.
Ann Harris
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

A critical cis-regulatory element for the CFTR (cystic fibrosis transmembrane conductance regulator) gene is located in intron 11, 100 kb distal to the promoter, with which it interacts. This sequence contains an intestine-selective enhancer and associates with enhancer signature proteins, such as p300, in addition to tissue-specific TFs (transcription factors). In the present study we identify critical TFs that are recruited to this element and demonstrate their importance in regulating CFTR expression. In vitro DNase I footprinting and EMSAs (electrophoretic mobility-shift assays) identified four cell-type-selective regions that bound TFs in vitro. ChIP (chromatin immunoprecipitation) identified FOXA1/A2 (forkhead box A1/A2), HNF1 (hepatocyte nuclear factor 1) and CDX2 (caudal-type homeobox 2) as in vivo trans-interacting factors. Mutation of their binding sites in the intron 11 core compromised its enhancer activity when measured by reporter gene assay. Moreover, siRNA (small interfering RNA)-mediated knockdown of CDX2 caused a significant reduction in endogenous CFTR transcription in intestinal cells, suggesting that this factor is critical for the maintenance of high levels of CFTR expression in these cells. The ChIP data also demonstrate that these TFs interact with multiple cis-regulatory elements across the CFTR locus, implicating a more global role in intestinal expression of the gene.

Indexed as

Enhancer Elements, GeneticCDX2 Transcription FactorCell LineCystic Fibrosis Transmembrane Conductance RegulatorEnterocytesForkhead Transcription FactorsGene Expression RegulationGenes, ReporterHepatocyte Nuclear Factor 1-alphaHomeodomain ProteinsHumansIntronsMutant ProteinsPeptide FragmentsProtein Interaction Domains and MotifsProtein IsoformsCDX2 protein, humanCDX2 Transcription FactorCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorForkhead Transcription FactorsHepatocyte Nuclear Factor 1-alphaHNF1A protein, humanHomeodomain ProteinsMutant ProteinsPeptide FragmentsProtein IsoformsRecombinant Fusion ProteinsRNA, MessengerRNA, Small InterferingTrans-Activators

Identifiers

PMID22671145
PMCPMC3419791
OpenAlexW2015659378

What OpenQuestion holds

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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.