Evidence map›Paper›PMID 32620778›Full record

ArticleNature communications2020

Comprehensive structure-function characterization of DNMT3B and DNMT3A reveals distinctive de novo DNA methylation mechanisms.

Linfeng Gao, Max Emperle, Yiran Guo, Sara A Grimm, Wendan Ren, Sabrina Adam, Hidetaka Uryu, Zhi-Min Zhang, Dongliang Chen, Jiekai Yin and 10 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed
8.9field-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

132 citing papers in PubMed, 190 citations in OpenAlex.

  1. Article
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  6. Multidomain interaction governs the filamentous assembly of the dominant-negative DNMT3A R882H mutant.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  16. Curcumin in High Doses Reverses the UV-B-InducedPharmaceuticals (Basel, Switzerland) · 2026
    Article
  17. Review
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  19. Article
  20. Article

72 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

20 authors at 4 institutions in 4 countries.

Linfeng Gao *Environmental Toxicology Graduate Program, University of California, Riverside, CA, 92521, USA.ORCID http://orcid.org/0000-0001-6194-5145
Max Emperle *Department of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Yiran Guo *Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27599, USA.ORCID http://orcid.org/0000-0002-6266-9186
Sara A GrimmDivision of Intramural Research, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, 27709, USA.
Wendan RenDepartment of Biochemistry, University of California, Riverside, CA, 92521, USA.ORCID http://orcid.org/0000-0002-0580-5321
Sabrina AdamDepartment of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Hidetaka UryuLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27599, USA.
Zhi-Min ZhangDepartment of Biochemistry, University of California, Riverside, CA, 92521, USA.ORCID http://orcid.org/0000-0002-5088-5869
Dongliang ChenLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27599, USA.
Jiekai YinEnvironmental Toxicology Graduate Program, University of California, Riverside, CA, 92521, USA.
Michael DukatzDepartment of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Hiwot AntenehDepartment of Biochemistry, University of California, Riverside, CA, 92521, USA.
Renata Z JurkowskaDepartment of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.ORCID http://orcid.org/0000-0002-4507-2222
Jiuwei LuDepartment of Biochemistry, University of California, Riverside, CA, 92521, USA.ORCID http://orcid.org/0000-0002-6478-4081
Yinsheng WangEnvironmental Toxicology Graduate Program, University of California, Riverside, CA, 92521, USA.
Pavel BashtrykovDepartment of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
Paul A WadeDivision of Intramural Research, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, 27709, USA.ORCID http://orcid.org/0000-0002-6042-357X
Gang Greg WangLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, 27599, USA. greg_wang@med.unc.edu.ORCID http://orcid.org/0000-0002-7210-9940
Albert JeltschDepartment of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany. albert.jeltsch@ibtb.uni-stuttgart.de.ORCID http://orcid.org/0000-0001-6113-9290
Jikui SongEnvironmental Toxicology Graduate Program, University of California, Riverside, CA, 92521, USA. jikui.song@ucr.edu.ORCID http://orcid.org/0000-0002-4958-1032
University of California, Riverside · USUniversity of Stuttgart · DEUniversity of North Carolina at Chapel Hill · USNational Institute of Environmental Health Sciences · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Deborah F. Tate · 1985 to 2026
$201.5M
Eukaryotic Transcriptional RegulationZIAES101965 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WADE, PAUL A · 2009 to 2025
$40.9M
Chemical Biology of DNA and RNA AlkylationR35ES031707 · NIEHS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Yinsheng Wang · 2020 to 2026
$6.1M
Mechanistic Insights into Mammalian DNA MethylationR35GM119721 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Jikui Song · 2016 to 2026
$5.3M
Eukaryotic Transcriptional RegulationZ01ES101965 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WADE, PAUL A · 2005 to 2008
$3.5M
Cancer Epigenetics: A novel PRC2 Dysregulation Mechanism in Multiple MyelomaR01CA211336 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WANG, G GREG · 2017 to 2021
$2.0M
Determining the Role of DNA Methylation Deregulation in OncogenesisR01CA215284 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WANG, G GREG · 2017 to 2021
$1.7M
Enzymatic Conversions of Tet-mediated Oxidation Products of 5-MethylcytosineR21ES025392 · NIEHS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI WANG, YINSHENG · 2015 to 2016
$425k
Intramural NIH HHS Z01 ES101965NCI NIH HHS P30 CA016086NCI NIH HHS R01 CA211336NCI NIH HHS R01 CA215284NIEHS NIH HHS R21 ES025392NIEHS NIH HHS R35 ES031707NIGMS NIH HHS R35 GM119721
6 · The paper itself

Abstract

Mammalian DNA methylation patterns are established by two de novo DNA methyltransferases, DNMT3A and DNMT3B, which exhibit both redundant and distinctive methylation activities. However, the related molecular basis remains undetermined. Through comprehensive structural, enzymology and cellular characterization of DNMT3A and DNMT3B, we here report a multi-layered substrate-recognition mechanism underpinning their divergent genomic methylation activities. A hydrogen bond in the catalytic loop of DNMT3B causes a lower CpG specificity than DNMT3A, while the interplay of target recognition domain and homodimeric interface fine-tunes the distinct target selection between the two enzymes, with Lysine 777 of DNMT3B acting as a unique sensor of the +1 flanking base. The divergent substrate preference between DNMT3A and DNMT3B provides an explanation for site-specific epigenomic alterations seen in ICF syndrome with DNMT3B mutations. Together, this study reveals distinctive substrate-readout mechanisms of the two DNMT3 enzymes, implicative of their differential roles during development and pathogenesis.

Indexed as

DNA MethylationAnimalsCatalytic DomainCell LineCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA Methyltransferase 3BEmbryonic Stem CellsEnzyme AssaysEpigenesis, GeneticFaceHumansMiceMutationPrimary Immunodeficiency DiseasesDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA Methyltransferase 3BDNMT3A protein, humanDnmt3a protein, mouse

Identifiers

PMID32620778
PMCPMC7335073
OpenAlexW3038200747

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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.