Evidence map›Paper›PMID 27270080›Full record

ArticleNucleic acids research2016

Differential sensitivity to methylated DNA by ETS-family transcription factors is intrinsically encoded in their DNA-binding domains.

Dominique C Stephens, Gregory M K Poon

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

29 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  4. DNA methylation shapes transcription factor binding beyond canonical CpG contexts.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

2 authors at 1 institution in 1 country.

Dominique C StephensDepartment of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
Gregory M K PoonDepartment of Chemistry, Georgia State University, Atlanta, GA 30303, USA Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA gpoon@gsu.edu.ORCID http://orcid.org/0000-0001-5107-9458
Georgia State University · US

Funding

Direct activation of hematopoietic transcription factorsR21HL129063 · NHLBI · GEORGIA STATE UNIVERSITY · PI POON, GREGORY MAN KAI · 2015 to 2016
$415k
NHLBI NIH HHS R21 HL129063
6 · The paper itself

Abstract

Transactivation by the ETS family of transcription factors, whose members share structurally conserved DNA-binding domains, is variably sensitive to methylation of their target genes. The mechanism by which DNA methylation controls ETS proteins remains poorly understood. Uncertainly also pervades the effects of hemi-methylated DNA, which occurs following DNA replication and in response to hypomethylating agents, on site recognition by ETS proteins. To address these questions, we measured the affinities of two sequence-divergent ETS homologs, PU.1 and Ets-1, to DNA sites harboring a hemi- and fully methylated CpG dinucleotide. While the two proteins bound unmethylated DNA with indistinguishable affinity, their affinities to methylated DNA are markedly heterogeneous and exhibit major energetic coupling between the two CpG methylcytosines. Analysis of simulated DNA and existing co-crystal structures revealed that hemi-methylation induced non-local backbone and groove geometries that were not conserved in the fully methylated state. Indirect readout of these perturbations was differentially achieved by the two ETS homologs, with the distinctive interfacial hydration in PU.1/DNA binding moderating the inhibitory effects of DNA methylation on binding. This data established a biophysical basis for the pioneering properties associated with PU.1, which robustly bound fully methylated DNA, but not Ets-1, which was substantially inhibited.

Indexed as

5-MethylcytosineAnimalsBinding SitesCpG IslandsDNADNA MethylationMiceNucleic Acid ConformationPrincipal Component AnalysisProtein BindingProtein DomainsProto-Oncogene ProteinsProto-Oncogene Proteins c-etsProto-Oncogene Protein Spi-1ThermodynamicsTrans-Activators5-MethylcytosineDNAProto-Oncogene ProteinsProto-Oncogene Proteins c-etsProto-Oncogene Protein Spi-1Trans-Activators

Identifiers

PMID27270080
PMCPMC5062964
OpenAlexW2416365174

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.