Evidence map›Paper›PMID 26123024›Full record

ArticleNature2015

Molecular basis for 5-carboxycytosine recognition by RNA polymerase II elongation complex.

Lanfeng Wang, Yu Zhou, Liang Xu, Rui Xiao, Xingyu Lu, Liang Chen, Jenny Chong, Hairi Li, Chuan He, Xiang-Dong Fu and 1 more

Abstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed
13.0field-weighted citation impact, top 1% 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

95 citing papers in PubMed, 155 citations in OpenAlex.

  1. Article
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  4. Review
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  9. Article
  10. Article
  11. A NiNature communications · 2024
    Article
  12. Article
  13. Review
  14. Review
  15. Micronutrient regulation of the DNA methylome.Frontiers in epigenetics and epigenomics · 2024
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Review

35 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Lanfeng WangSkaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Yu ZhouDepartment of Cellular and Molecular Medicine, School of Medicine, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Liang XuSkaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Rui XiaoDepartment of Cellular and Molecular Medicine, School of Medicine, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Xingyu LuDepartment of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637, USA.
Liang ChenDepartment of Cellular and Molecular Medicine, School of Medicine, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Jenny ChongSkaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Hairi LiDepartment of Cellular and Molecular Medicine, School of Medicine, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Chuan HeDepartment of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637, USA.
Xiang-Dong FuDepartment of Cellular and Molecular Medicine, School of Medicine, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Dong WangSkaggs School of Pharmacy and Pharmaceutical Sciences, The University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.
Howard Hughes Medical Institute · US

Funding

Functional RNA elements in the human genomeR01HG004659 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett, Eugene Wei-Ming Yeo · 2008 to 2026
$12.4M
Labeling and sequencing of 5hmC and 5mC in DNA-RenewalR01HG006827 · NHGRI · UNIVERSITY OF CHICAGO · PI HE, CHUAN · 2012 to 2025
$7.2M
Molecular Mechanisms for DNA Damage Processing by Transcription MachineryR01GM102362 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI WANG, DONG · 2013 to 2025
$5.6M
Regulation of RNA metabolism and cell growth control by SR protein kinasesR01GM052872 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DOWDY, STEVEN F · 1996 to 2019
$5.4M
Howard Hughes Medical InstituteNHGRI NIH HHS HG004659NHGRI NIH HHS HG006827NHGRI NIH HHS R01 HG004659NHGRI NIH HHS R01 HG006827NIGMS NIH HHS GM052872NIGMS NIH HHS GM102362NIGMS NIH HHS R01 GM052872NIGMS NIH HHS R01 GM102362
6 · The paper itself

Abstract

DNA methylation at selective cytosine residues (5-methylcytosine (5mC)) and their removal by TET-mediated DNA demethylation are critical for setting up pluripotent states in early embryonic development. TET enzymes successively convert 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), with 5fC and 5caC subject to removal by thymine DNA glycosylase (TDG) in conjunction with base excision repair. Early reports indicate that 5fC and 5caC could be stably detected on enhancers, promoters and gene bodies, with distinct effects on gene expression, but the mechanisms have remained elusive. Here we determined the X-ray crystal structure of yeast elongating RNA polymerase II (Pol II) in complex with a DNA template containing oxidized 5mCs, revealing specific hydrogen bonds between the 5-carboxyl group of 5caC and the conserved epi-DNA recognition loop in the polymerase. This causes a positional shift for incoming nucleoside 5'-triphosphate (NTP), thus compromising nucleotide addition. To test the implication of this structural insight in vivo, we determined the global effect of increased 5fC/5caC levels on transcription, finding that such DNA modifications indeed retarded Pol II elongation on gene bodies. These results demonstrate the functional impact of oxidized 5mCs on gene expression and suggest a novel role for Pol II as a specific and direct epigenetic sensor during transcription elongation.

Indexed as

Transcription Elongation, Genetic5-MethylcytosineCrystallography, X-RayCytosineDNA MethylationDNA RepairEpigenesis, GeneticHydrogen BondingKineticsRNA Polymerase IISaccharomyces cerevisiaeSubstrate SpecificityTemplates, GeneticThymine DNA Glycosylase5-carboxylcytosine5-formylcytosine5-hydroxymethylcytosine5-MethylcytosineCytosineRNA Polymerase IIThymine DNA Glycosylase

Identifiers

PMID26123024
PMCPMC4521995
OpenAlexW1770731112

What OpenQuestion holds

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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.