Evidence map›Paper›PMID 35346781›Full record

ArticleGenomics2022

Cross-talk between enhancers, structural elements and activating transcription factors maintains the 3D architecture and expression of the CFTR gene.

Shiyi Yin, Monali NandyMazumdar, Alekh Paranjapye, Ann Harris

Open access · goldAbstract read
In one paragraph

Article in Genomics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 30% 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

12 citing papers in PubMed, 11 citations in OpenAlex.

  1. Epigenetic regulation and chromatin organization in cystic fibrosis airways.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Tissue-Specific Regulation ofInternational journal of molecular sciences · 2023
    Review
  9. Cellular heterogeneity in the 16HBE14oPhysiological reports · 2023
    Article
  10. Article
  11. Article
  12. CFTR and Gastrointestinal Cancers: An Update.Journal of personalized medicine · 2022
    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.

Shiyi YinDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
Monali NandyMazumdarDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
Alekh ParanjapyeDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
Ann HarrisDepartment of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: ann.harris@case.edu.
Case Western Reserve University · US

Funding

GRADUATE TRAINING IN CELLULAR AND MOLECULAR BIOLOGYT32GM008056 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI DIEHL, JOHN ALAN, SNIDER, MARTIN D · 1985 to 2019
$7.1M
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 HL094585NICHD NIH HHS R01 HD068901NIGMS NIH HHS T32 GM008056
6 · The paper itself

Abstract

Robust protocols to examine 3D chromatin structure have greatly advanced knowledge of gene regulatory mechanisms. Here we focus on the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which provides a paradigm for validating models of gene regulation built upon genome-wide analysis. We examine the mechanisms by which multiple cis-regulatory elements (CREs) at the CFTR gene coordinate its expression in intestinal epithelial cells. Using CRISPR/Cas9 to remove CREs, individually and in tandem, followed by assays of gene expression and higher-order chromatin structure (4C-seq), we reveal the cross-talk and dependency of two cell-specific intronic enhancers. The results suggest a mechanism whereby the locus responds when CREs are lost, which may involve activating transcription factors such as FOXA2. Also, by removing the 5' topologically-associating domain (TAD) boundary, we illustrate its impact on CFTR gene expression and architecture. These data suggest a multi-layered regulatory hierarchy that is highly sensitive to perturbations.

Indexed as

Cystic Fibrosis Transmembrane Conductance RegulatorEnhancer Elements, GeneticActivating Transcription FactorsChromatinGene Expression RegulationActivating Transcription FactorsChromatinCystic Fibrosis Transmembrane Conductance Regulator3D chromatin architectureCis-regulatory elementsCystic fibrosis transmembrane conductance regulator (CFTR)EnhancersTopologically associated domain (TAD) boundariesTranscription factors

Identifiers

PMID35346781
PMCPMC9509493
OpenAlexW4220978287

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.