Evidence map›Paper›PMID 25258363›Full record

ArticleGenes & development2014

Wilms tumor protein recognizes 5-carboxylcytosine within a specific DNA sequence.

Hideharu Hashimoto, Yusuf Olatunde Olanrewaju, Yu Zheng, Geoffrey G Wilson, Xing Zhang, Xiaodong Cheng

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
–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, 132 citations in OpenAlex.

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  14. Role of early growth response 1 in inflammation-associated lung diseases.American journal of physiology. Lung cellular and molecular physiology · 2023
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Mechanisms that regulate the activities of TET proteins.Cellular and molecular life sciences : CMLS · 2022
    Review
  20. ACS physical chemistry Au · 2022
    Article

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

6 authors at 2 institutions in 1 country.

Hideharu HashimotoDepartment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA;
Yusuf Olatunde OlanrewajuDepartment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA;
Yu ZhengNew England Biolabs, Ipswich, Massachusetts 01938, USA.
Geoffrey G WilsonNew England Biolabs, Ipswich, Massachusetts 01938, USA.
Xing ZhangDepartment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA;
Xiaodong ChengDepartment of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA; xcheng@emory.edu.
Emory University · USNew England Biolabs (United States) · US

Funding

THREE-DIMENSIONAL STRUCTURE OF HHAI METHYLASER01GM049245 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHENG, XIAODONG · 1993 to 2017
$6.6M
NIGMS NIH HHS GM049245-21NIGMS NIH HHS R01 GM049245
6 · The paper itself

Abstract

In mammalian DNA, cytosine occurs in several chemical forms, including unmodified cytosine (C), 5-methylcytosine (5 mC), 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5 fC), and 5-carboxylcytosine (5 caC). 5 mC is a major epigenetic signal that acts to regulate gene expression. 5 hmC, 5 fC, and 5 caC are oxidized derivatives that might also act as distinct epigenetic signals. We investigated the response of the zinc finger DNA-binding domains of transcription factors early growth response protein 1 (Egr1) and Wilms tumor protein 1 (WT1) to different forms of modified cytosine within their recognition sequence, 5'-GCG(T/G)GGGCG-3'. Both displayed high affinity for the sequence when C or 5 mC was present and much reduced affinity when 5 hmC or 5 fC was present, indicating that they differentiate primarily oxidized C from unoxidized C, rather than methylated C from unmethylated C. 5 caC affected the two proteins differently, abolishing binding by Egr1 but not by WT1. We ascribe this difference to electrostatic interactions in the binding sites. In Egr1, a negatively charged glutamate conflicts with the negatively charged carboxylate of 5 caC, whereas the corresponding glutamine of WT1 interacts with this group favorably. Our analyses shows that zinc finger proteins (and their splice variants) can respond in modulated ways to alternative modifications within their binding sequence.

Indexed as

CrystallizationCytosineDNA MethylationEarly Growth Response Protein 1HumansModels, MolecularMutationOxidation-ReductionProtein BindingProtein Structure, TertiaryWT1 Proteins5-carboxylcytosineCytosineEarly Growth Response Protein 1EGR1 protein, humanWT1 protein, humanWT1 Proteins5-carboxylcytosineDNA modificationepigenetics

Identifiers

PMID25258363
PMCPMC4201290
OpenAlexW2114716625

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.