Evidence map›Paper›PMID 33542217›Full record

ArticleNature communications2021

An all-to-all approach to the identification of sequence-specific readers for epigenetic DNA modifications on cytosine.

Guang Song, Guohua Wang, Ximei Luo, Ying Cheng, Qifeng Song, Jun Wan, Cedric Moore, Hongjun Song, Peng Jin, Jiang Qian and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.1field-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

23 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Guang Song *Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-7630-716X
Guohua Wang *School of Computer Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, China.ORCID http://orcid.org/0000-0001-7381-2374
Ximei Luo *School of Computer Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang, China.ORCID http://orcid.org/0000-0003-2956-6799
Ying ChengDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Qifeng SongDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jun WanDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-9286-6562
Cedric MooreDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hongjun SongDepartment of Neuroscience and Mahoney Institute for Neurosciences, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8720-5310
Peng JinDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.ORCID http://orcid.org/0000-0001-6137-6659
Jiang QianDepartment of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. jiang.qian@jhmi.edu.ORCID http://orcid.org/0000-0002-0476-3596
Heng ZhuDepartment of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. hzhu4@jhmi.edu.ORCID http://orcid.org/0000-0002-8426-2889
Johns Hopkins University · USEmory University · USHarbin Institute of Technology · CNUniversity of Pennsylvania · US

Funding

Molecular Basis of rCGG-Mediated NeurodegenerationR01NS051630 · NINDS · EMORY UNIVERSITY · PI NELSON, DAVID LOREN · 2006 to 2023
$9.8M
Continuous Neurogenesis in the Mammalian HippocampusR35NS116843 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI HONGJUN SONG · 2020 to 2026
$6.9M
Clinical Resources for Alcoholic Hepatitis InvestigationsR24AA025017 · NIAAA · JOHNS HOPKINS UNIVERSITY · PI ZHAOLI SUN · 2016 to 2026
$6.6M
Dynamic DNA Modifications in Brain and DiseasesR35NS111602 · NINDS · EMORY UNIVERSITY · PI PENG JIN · 2019 to 2026
$6.5M
Translational models of neurodevelopmental epigenetics and disease using human iPSCsP01NS097206 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI HE, CHUAN · 2016 to 2020
$4.3M
The Chemistry-Biology Interface Program at Johns Hopkins UniversityT32GM080189 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ROKITA, STEVEN E · 2008 to 2022
$3.5M
High-throughput identification of causal variants underlying neuropsychiatric disease-related GWAS hitsR01MH122451 · NIMH · WASHINGTON UNIVERSITY · PI CORBO, JOSEPH · 2020 to 2024
$3.5M
High-throughput identification of causal variants underlying cardiac arrhythmia-related GWAS hitsR01HL149961 · NHLBI · WASHINGTON UNIVERSITY · PI CORBO, JOSEPH · 2020 to 2023
$2.9M
Development of in vitro diagnostic multivariate index assay using liquid-based cervical cytology specimen and/or serum/plasma biomarkers for the detection of early stage or low-volume ovarian cancerU01CA200469 · NCI · JOHNS HOPKINS UNIVERSITY · PI SHIH, IE-MING, ZHANG, ZHEN · 2016 to 2021
$2.9M
Proteome-wide analysis of AD-associated SNPsR01AG061852 · NIA · JOHNS HOPKINS UNIVERSITY · PI ZHU, HENG · 2018 to 2022
$2.8M
Computational Tools for Single Cell Analysis: Application to Retinal DegenerationR01EY029548 · NEI · JOHNS HOPKINS UNIVERSITY · PI QIAN, JIANG, ZACK, DONALD J. · 2018 to 2021
$1.6M
Differential Regulatory Networks in Disease: Application to Macular DegenerationR01EY024580 · NEI · JOHNS HOPKINS UNIVERSITY · PI QIAN, JIANG · 2014 to 2017
$1.6M
NCI NIH HHS U01 CA200469NEI NIH HHS R01 EY024580NEI NIH HHS R01 EY029548NHLBI NIH HHS R01 HL149961NIAAA NIH HHS R24 AA025017NIA NIH HHS R01 AG061852NIGMS NIH HHS R01 GM111514NIGMS NIH HHS T32 GM080189NIMH NIH HHS R01 MH122451NINDS NIH HHS P01 NS097206NINDS NIH HHS R01 NS051630NINDS NIH HHS R35 NS111602NINDS NIH HHS R35 NS116843
6 · The paper itself

Abstract

Epigenetic modifications of DNA play important roles in many biological processes. Identifying readers of these epigenetic marks is a critical step towards understanding the underlying mechanisms. Here, we present an all-to-all approach, dubbed digital affinity profiling via proximity ligation (DAPPL), to simultaneously profile human TF-DNA interactions using mixtures of random DNA libraries carrying different epigenetic modifications (i.e., 5-methylcytosine, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine) on CpG dinucleotides. Many proteins that recognize consensus sequences carrying these modifications in symmetric and/or hemi-modified forms are identified. We further demonstrate that the modifications in different sequence contexts could either enhance or suppress TF binding activity. Moreover, many modifications can affect TF binding specificity. Furthermore, symmetric modifications show a stronger effect in either enhancing or suppressing TF-DNA interactions than hemi-modifications. Finally, in vivo evidence suggests that USF1 and USF2 might regulate transcription via hydroxymethylcytosine-binding activity in weak enhancers in human embryonic stem cells.

Indexed as

5-MethylcytosineCell LineCpG IslandsDNAEnhancer Elements, GeneticEpigenesis, GeneticEpigenomicsGene LibraryHuman Embryonic Stem CellsHumansRecombinant ProteinsUpstream Stimulatory Factors5-hydroxymethylcytosine5-MethylcytosineDNARecombinant ProteinsUpstream Stimulatory FactorsUSF1 protein, humanUSF2 protein, human

Identifiers

PMID33542217
PMCPMC7862700
OpenAlexW3127255754

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.