Evidence map›Paper›PMID 27485769›Full record

ArticleIntegrative biology : quantitative biosciences from nano to macro2016

5-Hydroxymethylcytosine in E-box motifs ACAT|GTG and ACAC|GTG increases DNA-binding of the B-HLH transcription factor TCF4.

Syed Khund-Sayeed, Ximiao He, Timothy Holzberg, Jun Wang, Divya Rajagopal, Shriyash Upadhyay, Stewart R Durell, Sanjit Mukherjee, Matthew T Weirauch, Robert Rose and 1 more

Open access · greenAbstract read
In one paragraph

Article in Integrative biology : quantitative biosciences from nano to macro, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Cell identity and 5-hydroxymethylcytosine.Epigenetics & chromatin · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. The bZIP mutant CEBPB (V285A) has sequence specific DNA binding propensities similar to CREB1.Biochimica et biophysica acta. Gene regulatory mechanisms · 2019
    Article
  13. Article
  14. Comprehensive, high-resolution binding energy landscapes reveal context dependencies of transcription factor binding.Proceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  15. Review
  16. Article
  17. TET proteins in natural and induced differentiation.Current opinion in genetics & development · 2017
    Review
  18. Article
  19. Article
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

11 authors at 6 institutions in 2 countries.

Syed Khund-SayeedLaboratory of Metabolism, National Cancer Institute, National Institutes of Health, Room 3128, Building 37, Bethesda, MD 20892, USA. vinsonc@mail.nih.gov.
Ximiao He
Timothy Holzberg
Jun Wang
Divya Rajagopal
Shriyash Upadhyay
Stewart R Durell
Sanjit Mukherjee
Matthew T Weirauch
Robert Rose
Charles Vinson
In-Q-Tel · USNational Institutes of Health · USNational Cancer Institute · USNorth Carolina State University · USState Key Laboratory of Cell BiologyUniversity of Cincinnati · US

Funding

Effects of Cytosine Modifications on Transcription Factor BindingZICBC011724 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI DURELL, STEWART · 2016 to 2023
$961k
Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

We evaluated DNA binding of the B-HLH family members TCF4 and USF1 using protein binding microarrays (PBMs) containing double-stranded DNA probes with cytosine on both strands or 5-methylcytosine (5mC) or 5-hydroxymethylcytosine (5hmC) on one DNA strand and cytosine on the second strand. TCF4 preferentially bound the E-box motif (CAN|NTG) with strongest binding to the 8-mer CAG|GTGGT. 5mC uniformly decreases DNA binding of both TCF4 and USF1. The bulkier 5hmC also inhibited USF1 binding to DNA. In contrast, 5hmC dramatically enhanced TCF4 binding to E-box motifs ACAT|GTG and ACAC|GTG, being better bound than any 8-mer containing cytosine. Examination of X-ray structures of the closely related TCF3 and USF1 bound to DNA suggests TCF3 can undergo a conformational shift to preferentially bind to 5hmC while the USF1 basic region is bulkier and rigid precluding a conformation shift to bind 5hmC. These results greatly expand the regulatory DNA sequence landscape bound by TCF4.

Indexed as

E-Box Elements5-MethylcytosineBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBinding SitesDNADNA-Binding ProteinsProtein Array AnalysisProtein BindingProtein Interaction Domains and MotifsProtein Interaction MappingTranscription Factor 45-hydroxymethylcytosine5-MethylcytosineBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsDNADNA-Binding ProteinsTCF4 protein, humanTranscription Factor 4

Identifiers

PMID27485769
PMCPMC6289052
OpenAlexW2477608521

What OpenQuestion holds

Textmetadata
LicenceTDM
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.