Evidence map›Paper›PMID 22951069›Full record

ArticleGenome biology2012

Cell type-specific binding patterns reveal that TCF7L2 can be tethered to the genome by association with GATA3.

Seth Frietze, Rui Wang, Lijing Yao, Yu Gyoung Tak, Zhenqing Ye, Malaina Gaddis, Heather Witt, Peggy J Farnham, Victor X Jin

Abstract read
In one paragraph

Article in Genome biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

85 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Differential Wnt/β-catenin signaling via TCF7L2/LEF1 binding specificity shapes cellular and tumor phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Wnt/β-catenin signaling pathway in liver biology and tumorigenesis.In vitro cellular & developmental biology. Animal · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Characteristics of the TDRD1 gene promoter in chickens.Molecular genetics and genomics : MGG · 2022
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Epigenetic regulation of intestinal stem cell differentiation.American journal of physiology. Gastrointestinal and liver physiology · 2020
    Review
  20. Aging · 2020
    Observational

25 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

9 authors.

Seth FrietzeDepartment of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90089, USA.
Rui Wang
Lijing Yao
Yu Gyoung Tak
Zhenqing Ye
Malaina Gaddis
Heather Witt
Peggy J Farnham
Victor X Jin

Funding

USC/NORRIS COMPREHENSIVE CANCER CENTER (CORE) SUPPORTP30CA014089 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MYLES G COCKBURN · 1985 to 2026
$181.4M
Production Center for Global Mapping of Regulatory ElementsU54HG004558 · NHGRI · YALE UNIVERSITY · PI SNYDER, MICHAEL P. · 2007 to 2011
$15.4M
NCI NIH HHS P30CA014089NHGRI NIH HHS 1U54HG004558
6 · The paper itself

Abstract

backgroundThe TCF7L2 transcription factor is linked to a variety of human diseases, including type 2 diabetes and cancer. One mechanism by which TCF7L2 could influence expression of genes involved in diverse diseases is by binding to distinct regulatory regions in different tissues. To test this hypothesis, we performed ChIP-seq for TCF7L2 in six human cell lines.

resultsWe identified 116,000 non-redundant TCF7L2 binding sites, with only 1,864 sites common to the six cell lines. Using ChIP-seq, we showed that many genomic regions that are marked by both H3K4me1 and H3K27Ac are also bound by TCF7L2, suggesting that TCF7L2 plays a critical role in enhancer activity. Bioinformatic analysis of the cell type-specific TCF7L2 binding sites revealed enrichment for multiple transcription factors, including HNF4alpha and FOXA2 motifs in HepG2 cells and the GATA3 motif in MCF7 cells. ChIP-seq analysis revealed that TCF7L2 co-localizes with HNF4alpha and FOXA2 in HepG2 cells and with GATA3 in MCF7 cells. Interestingly, in MCF7 cells the TCF7L2 motif is enriched in most TCF7L2 sites but is not enriched in the sites bound by both GATA3 and TCF7L2. This analysis suggested that GATA3 might tether TCF7L2 to the genome at these sites. To test this hypothesis, we depleted GATA3 in MCF7 cells and showed that TCF7L2 binding was lost at a subset of sites. RNA-seq analysis suggested that TCF7L2 represses transcription when tethered to the genome via GATA3.

conclusionsOur studies demonstrate a novel relationship between GATA3 and TCF7L2, and reveal important insights into TCF7L2-mediated gene regulation.

Indexed as

Genome, HumanTranscription, GeneticBinding SitesCell Line, TumorEnhancer Elements, GeneticGATA3 Transcription FactorHEK293 CellsHepatocyte Nuclear Factor 3-betaHepatocyte Nuclear Factor 4HumansNucleotide MotifsOrgan SpecificityProtein BindingTranscription Factor 7-Like 2 ProteinFOXA2 protein, humanGATA3 protein, humanGATA3 Transcription FactorHepatocyte Nuclear Factor 3-betaHepatocyte Nuclear Factor 4HNF4A protein, humanTCF7L2 protein, humanTranscription Factor 7-Like 2 Protein

Identifiers

PMID22951069
PMCPMC3491396

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.