Evidence map›Paper›PMID 28850571›Full record

ArticlePLoS biology2017

Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells.

Colin R Lickwar, J Gray Camp, Matthew Weiser, Jordan L Cocchiaro, David M Kingsley, Terrence S Furey, Shehzad Z Sheikh, John F Rawls

Open access · goldAbstract readComparative Study
In one paragraph

Article in PLoS biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
8.1field-weighted citation impact, top 2% 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

72 citing papers in PubMed, 134 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. TheMicrobiology and molecular biology reviews : MMBR · 2025
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Beyond Rodents: Alternative Animal Models in Colorectal Cancer Research.International journal of molecular sciences · 2025
    Review
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review

12 more citing papers are in PubMed but not listed here.

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

8 authors at 2 institutions in 1 country.

Colin R LickwarDepartment of Molecular Genetics and Microbiology, Center for the Genomics of Microbial Systems, Duke University, Durham, North Carolina, United States of America.ORCID http://orcid.org/0000-0002-7312-6291
J Gray CampDepartment of Cell Biology and Physiology, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Matthew WeiserDepartments of Genetics and Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Jordan L CocchiaroDepartment of Molecular Genetics and Microbiology, Center for the Genomics of Microbial Systems, Duke University, Durham, North Carolina, United States of America.
David M KingsleyDepartment of Developmental Biology, Stanford University, Stanford, California, United States of America.
Terrence S FureyDepartments of Genetics and Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Shehzad Z SheikhDepartment of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
John F RawlsDepartment of Molecular Genetics and Microbiology, Center for the Genomics of Microbial Systems, Duke University, Durham, North Carolina, United States of America.
University of North Carolina at Chapel Hill · USStanford University · US

Funding

Genomic Basis of Vertebrate DiversityP50HG002568 · NHGRI · STANFORD UNIVERSITY · PI KINGSLEY, DAVID M · 2002 to 2011
$29.2M
Role of IL-10 in APC Regulation of Protective vs. Pathogenic T Cell Responses toP01DK094779 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SARTOR, RYAN B · 2013 to 2023
$17.9M
Identifying genes required for digestive physiology and lipid metabolismR01DK093399 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI STEVEN A FARBER, John F Rawls · 2013 to 2026
$7.6M
Immune Compromises Zebrafish for Cell TransplantationR24OD016761 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI LANGENAU, DAVID MICHAEL · 2013 to 2021
$5.2M
Microbial Regulation of Host Nutrient MetabolismR01DK081426 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI RAWLS, JOHN F · 2008 to 2019
$3.9M
Integrative Genetic and Genomic Analyses in the Inflammatory Bowel DiseaseR01DK104828 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FUREY, TERRENCE S., SHEIKH, SHEHZAD Z. · 2016 to 2018
$901k
NHGRI NIH HHS P50 HG002568NIDDK NIH HHS P01 DK094779NIDDK NIH HHS R01 DK081426NIDDK NIH HHS R01 DK093399NIDDK NIH HHS R01 DK104828NIH HHS R24 OD016761
6 · The paper itself

Abstract

The intestinal epithelium serves critical physiologic functions that are shared among all vertebrates. However, it is unknown how the transcriptional regulatory mechanisms underlying these functions have changed over the course of vertebrate evolution. We generated genome-wide mRNA and accessible chromatin data from adult intestinal epithelial cells (IECs) in zebrafish, stickleback, mouse, and human species to determine if conserved IEC functions are achieved through common transcriptional regulation. We found evidence for substantial common regulation and conservation of gene expression regionally along the length of the intestine from fish to mammals and identified a core set of genes comprising a vertebrate IEC signature. We also identified transcriptional start sites and other putative regulatory regions that are differentially accessible in IECs in all 4 species. Although these sites rarely showed sequence conservation from fish to mammals, surprisingly, they drove highly conserved IEC expression in a zebrafish reporter assay. Common putative transcription factor binding sites (TFBS) found at these sites in multiple species indicate that sequence conservation alone is insufficient to identify much of the functionally conserved IEC regulatory information. Among the rare, highly sequence-conserved, IEC-specific regulatory regions, we discovered an ancient enhancer upstream from her6/HES1 that is active in a distinct population of Notch-positive cells in the intestinal epithelium. Together, these results show how combining accessible chromatin and mRNA datasets with TFBS prediction and in vivo reporter assays can reveal tissue-specific regulatory information conserved across 420 million years of vertebrate evolution. We define an IEC transcriptional regulatory network that is shared between fish and mammals and establish an experimental platform for studying how evolutionarily distilled regulatory information commonly controls IEC development and physiology.

Indexed as

Gene Expression RegulationAnimalsCaliforniaColonDuodenumFemaleFish ProteinsGene Expression ProfilingGenomicsHumansIleumIntestinal MucosaJejunumLarvaMaleMiceFish ProteinsRNA, Messenger

Identifiers

PMID28850571
PMCPMC5574553
OpenAlexW2752849791

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.