Evidence map›Paper›PMID 28916725›Full record

ArticleThe Journal of biological chemistry2017

Characterization of enhancers and the role of the transcription factor KLF7 in regulating corneal epithelial differentiation.

Rachel Herndon Klein, William Hu, Ghaidaa Kashgari, Ziguang Lin, Tuyen Nguyen, Michael Doan, Bogi Andersen

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

23 citing papers in PubMed, 33 citations in OpenAlex.

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  9. Molecular function of Krüppel-like factor 7 in biology.Acta biochimica et biophysica Sinica · 2023
    Review
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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

7 authors at 1 institution in 1 country.

Rachel Herndon KleinFrom the Departments of Biological Chemistry and.
William HuFrom the Departments of Biological Chemistry and.
Ghaidaa KashgariFrom the Departments of Biological Chemistry and.
Ziguang LinFrom the Departments of Biological Chemistry and.
Tuyen NguyenFrom the Departments of Biological Chemistry and.
Michael DoanFrom the Departments of Biological Chemistry and.
Bogi AndersenFrom the Departments of Biological Chemistry and bogi@uci.edu.
University of California, Irvine · US

Funding

Transcriptional Co-Regulators in EpidermisR01AR044882 · NIAMS · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI Bogi Andersen · 1998 to 2026
$9.0M
CARCINOGENESIST32CA009054 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI EDINGER, AIMEE L, FRUMAN, DAVID ALEXANDER · 1985 to 2025
$8.6M
Epithelial differentiation in corneaR01EY019413 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI ANDERSEN, BOGI · 2009 to 2012
$1.4M
NCI NIH HHS T32 CA009054NEI NIH HHS R01 EY019413NIAMS NIH HHS R01 AR044882
6 · The paper itself

Abstract

During tissue development, transcription factors bind regulatory DNA regions called enhancers, often located at great distances from the genes they regulate, to control gene expression. The enhancer landscape during embryonic stem cell differentiation has been well characterized. By contrast, little is known about the shared and unique enhancer regulatory mechanisms in different ectodermally derived epithelial cells. Here we use ChIP sequencing (ChIP-seq) to identify domains enriched for the histone marks histone H3 lysine 4 trimethylation, histone H3 lysine 4 monomethylation, and histone H3 lysine 27 acetylation (H3K4me3, H3K4me1, and H3K27ac) and define, for the first time, the super enhancers and typical enhancers active in primary human corneal epithelial cells. We show that regulatory regions are often shared between cell types of the ectodermal lineage and that corneal epithelial super enhancers are already marked as potential regulatory domains in embryonic stem cells. Kruppel-like factor (KLF) motifs were enriched in corneal epithelial enhancers, consistent with the important roles of KLF4 and KLF5 in promoting corneal epithelial differentiation. We now show that the Kruppel family member KLF7 promotes the corneal progenitor cell state; on many genes, KLF7 antagonized the corneal differentiation-promoting KLF4. Furthermore, we found that two SNPs linked previously to corneal diseases, astigmatism, and Stevens-Johnson syndrome fall within corneal epithelial enhancers and alter their activity by disrupting transcription factor motifs that overlap these SNPs. Taken together, our work defines regulatory enhancers in corneal epithelial cells, highlights global gene-regulatory relationships shared among different epithelial cells, identifies a role for KLF7 as a KLF4 antagonist in corneal epithelial cell differentiation, and explains how two SNPs may contribute to corneal diseases.

Indexed as

Cell DifferentiationEnhancer Elements, GeneticGene Expression RegulationAcetylationCell LineChromatin ImmunoprecipitationCorneal DiseasesEpithelium, CornealHistonesHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsPolymorphism, Single NucleotideStem CellsHistonesKLF4 protein, humanKLF7 protein, humanKruppel-Like Factor 4Kruppel-Like Transcription Factorscell proliferationchromatincorneal epitheliumepithelial celleyegene regulationKLF7Kruppel-like factor 4 (KLF4)superenhancer

Identifiers

PMID28916725
PMCPMC5704477
OpenAlexW2755391623

What Socratic 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 Socratic graph.