Evidence map›Paper›PMID 25414359›Full record

ArticleNucleic acids research2014

The TCF C-clamp DNA binding domain expands the Wnt transcriptome via alternative target recognition.

Nate P Hoverter, Michael D Zeller, Miriam M McQuade, Angela Garibaldi, Anke Busch, Elizabeth M Selwan, Klemens J Hertel, Pierre Baldi, Marian L Waterman

Abstract read
In one paragraph

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 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. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. 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

9 authors.

Nate P HoverterDepartment of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697, USA.
Michael D ZellerDepartment of Information and Computer Science, University of California, Irvine, Irvine, CA 92697, USA.
Miriam M McQuadeDepartment of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697, USA.
Angela GaribaldiDepartment of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697, USA.
Anke BuschDepartment of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697, USA.
Elizabeth M SelwanDepartment of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697, USA.
Klemens J HertelDepartment of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697, USA.
Pierre BaldiDepartment of Information and Computer Science, University of California, Irvine, Irvine, CA 92697, USA.
Marian L WatermanDepartment of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697, USA marian.waterman@uci.edu.

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Biomedical Informatics Training ProgramT15LM007443 · NLM · UNIVERSITY OF CALIFORNIA-IRVINE · PI BALDI, PIERRE · 2002 to 2012
$9.3M
Characterization of the mammalian mRNA-3'-end processing complexR01GM090056 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI SHI, YONGSHENG · 2010 to 2022
$4.2M
LEF/TCF Expression in Colon CancerR01CA096878 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI WATERMAN, MARIAN L · 2003 to 2012
$2.7M
Wnt Signaling in Colon CancerR01CA108697 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI WATERMAN, MARIAN L · 2005 to 2015
$2.7M
Coordinated regulation of alternative pre-mRNA processing in colon cancerR01CA177651 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI EDWARDS, ROBERT ANDREW, HERTEL, KLEMENS J · 2014 to 2018
$2.4M
Characterizing aberrant alternative-splicing in breast cancerF31CA171791 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI GARIBALDI, ANGELA · 2012 to 2015
$143k
NCI NIH HHS CA096878NCI NIH HHS CA108697NCI NIH HHS CA177651NCI NIH HHS F31 CA171791NCI NIH HHS P30 CA062203NCI NIH HHS P30CA062203NCI NIH HHS R01 CA096878NCI NIH HHS R01 CA108697NCI NIH HHS R01CA108697NCI NIH HHS R01 CA177651NIGMS NIH HHS R01 GM090056NLM NIH HHS T15LM07443
6 · The paper itself

Abstract

LEF/TCFs direct the final step in Wnt/β-catenin signalling by recruiting β-catenin to genes for activation of transcription. Ancient, non-vertebrate TCFs contain two DNA binding domains, a High Mobility Group box for recognition of the Wnt Response Element (WRE; 5'-CTTTGWWS-3') and the C-clamp domain for recognition of the GC-rich Helper motif (5'-RCCGCC-3'). Two vertebrate TCFs (TCF-1/TCF7 and TCF-4/TCF7L2) use the C-clamp as an alternatively spliced domain to regulate cell-cycle progression, but how the C-clamp influences TCF binding and activity genome-wide is not known. Here, we used a doxycycline inducible system with ChIP-seq to assess how the C-clamp influences human TCF1 binding genome-wide. Metabolic pulse-labeling of nascent RNA with 4'Thiouridine was used with RNA-seq to connect binding to the Wnt transcriptome. We find that the C-clamp enables targeting to a greater number of gene loci for stronger occupancy and transcription regulation. The C-clamp uses Helper sites concurrently with WREs for gene targeting, but it also targets TCF1 to sites that do not have readily identifiable canonical WREs. The coupled ChIP-seq/4'Thiouridine-seq analysis identified new Wnt target genes, including additional regulators of cell proliferation. Thus, C-clamp containing isoforms of TCFs are potent transcriptional regulators with an expanded transcriptome directed by C-clamp-Helper site interactions.

Indexed as

TranscriptomeWnt Signaling PathwayAnimalsCell Line, TumorChlorocebus aethiopsChromatin ImmunoprecipitationCOS CellsDNAGene Expression RegulationGenetic LociHepatocyte Nuclear Factor 1-alphaHumansMutationNucleotide MotifsProtein BindingProtein Structure, TertiaryDNAHepatocyte Nuclear Factor 1-alphaHNF1A protein, humanThiouridine

Identifiers

PMID25414359
PMCPMC4267635

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.