Evidence map›Paper›PMID 27027282›Full record

ArticleNature2016

DNA methylation on N(6)-adenine in mammalian embryonic stem cells.

Tao P Wu, Tao Wang, Matthew G Seetin, Yongquan Lai, Shijia Zhu, Kaixuan Lin, Yifei Liu, Stephanie D Byrum, Samuel G Mackintosh, Mei Zhong and 6 more

Abstract read
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 332 papers.

0numbers the graph read from it
0cells of the map it votes in
332citing papers in PubMed
42.8field-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

332 citing papers in PubMed, 663 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. mBiology direct · 2026
    Review
  5. Integration of epigenetics into ecotoxicology: insights and fundamental research needs.Biological reviews of the Cambridge Philosophical Society · 2026
    Review
  6. Article
  7. A distinct subclade of AlkB family demethylases in ciliates safeguards the positional fidelity of eukaryotic NProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  8. N6-methyladenine DNA modification modulates pathogen virulence in nematodes.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 1 country.

Tao P WuDepartment of Genetics and Yale Stem Cell Center, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Tao WangDepartment of Genetics and Yale Stem Cell Center, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Matthew G SeetinPacific Biosciences, 1380 Willow Road, Menlo Park, California 94025, USA.
Yongquan LaiEnvironmental Sciences &Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Shijia ZhuDepartment of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York 10029, USA.
Kaixuan LinDepartment of Genetics and Yale Stem Cell Center, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Yifei LiuDepartment of Genetics and Yale Stem Cell Center, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Stephanie D ByrumDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Samuel G MackintoshDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Mei ZhongYale Stem Cell Center and Department of Cell Biology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Alan TackettDepartment of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Guilin WangDepartment of Molecular Biophysics &Biochemistry, Yale Center for Genome Analysis, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Lawrence S HonPacific Biosciences, 1380 Willow Road, Menlo Park, California 94025, USA.
Gang FangDepartment of Genetics and Genomic Sciences and Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York 10029, USA.
James A SwenbergEnvironmental Sciences &Engineering, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Andrew Z XiaoDepartment of Genetics and Yale Stem Cell Center, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Yale Cancer Center · USUniversity of Arkansas for Medical Sciences · USIcahn School of Medicine at Mount Sinai · USPacific Biosciences (United States) · USUniversity of North Carolina at Chapel Hill · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
Understanding Hesitant AdoptersP20GM103429 · NIGMS · UNIV OF ARKANSAS FOR MED SCIS · PI Lawrence E Cornett, JERRY WARE · 2012 to 2026
$60.9M
STOCHASTIC ANALYSIS OF FLOW AND TRANSPORT PHENOMENAP42ES005948 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FRY, REBECCA · 1992 to 2017
$45.4M
UNC-CH CENTER FOR ENVIRONMENTAL HEALTH &SUSCEPTIBILITYP30ES010126 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Melissa A. Troester · 2001 to 2026
$36.3M
Methods for Multiscale and Integrative Characterization of Bacterial EpigenomesR01GM114472 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FANG, GANG · 2015 to 2019
$2.1M
Investigate Novel Epigenetic Silencing Mechanisms in Mouse ESCsR01GM114205 · NIGMS · YALE UNIVERSITY · PI XIAO, ZHUO ANDREW · 2015 to 2019
$2.1M
Using ChAP-MS to Study Macromolecular Chromatin Composition during TranscriptionR01GM106024 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI TACKETT, ALAN, TAVERNA, SEAN D. · 2013 to 2016
$1.2M
Orbitrap Fusion Tribrid Mass SpectrometerS10OD018445 · OD · UNIV OF ARKANSAS FOR MED SCIS · PI MACKINTOSH, SAMUEL G. · 2015 to 2015
$856k
NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA016359NIEHS NIH HHS P30 ES010126NIEHS NIH HHS P42 ES005948NIGMS NIH HHS P20 GM103429NIGMS NIH HHS P20GM103429NIGMS NIH HHS R01 GM106024NIGMS NIH HHS R01GM106024NIGMS NIH HHS R01 GM114205NIGMS NIH HHS R01GM114205-01NIGMS NIH HHS R01 GM114472NIGMS NIH HHS R01 GM114472-01NIH HHS S10 OD018445NIH HHS S10OD018445
6 · The paper itself

Abstract

It has been widely accepted that 5-methylcytosine is the only form of DNA methylation in mammalian genomes. Here we identify N(6)-methyladenine as another form of DNA modification in mouse embryonic stem cells. Alkbh1 encodes a demethylase for N(6)-methyladenine. An increase of N(6)-methyladenine levels in Alkbh1-deficient cells leads to transcriptional silencing. N(6)-methyladenine deposition is inversely correlated with the evolutionary age of LINE-1 transposons; its deposition is strongly enriched at young (<1.5 million years old) but not old (>6 million years old) L1 elements. The deposition of N(6)-methyladenine correlates with epigenetic silencing of such LINE-1 transposons, together with their neighbouring enhancers and genes, thereby resisting the gene activation signals during embryonic stem cell differentiation. As young full-length LINE-1 transposons are strongly enriched on the X chromosome, genes located on the X chromosome are also silenced. Thus, N(6)-methyladenine developed a new role in epigenetic silencing in mammalian evolution distinct from its role in gene activation in other organisms. Our results demonstrate that N(6)-methyladenine constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes.

Indexed as

DNA MethylationAdenineAlkB Homolog 1, Histone H2a DioxygenaseAnimalsCell DifferentiationDNA-(Apurinic or Apyrimidinic Site) LyaseDNA Transposable ElementsEnhancer Elements, GeneticEpigenesis, GeneticEvolution, MolecularGene SilencingLong Interspersed Nucleotide ElementsMammalsMiceMouse Embryonic Stem CellsUp-Regulation6-methyladenineAdenineAlkbh1 protein, mouseAlkB Homolog 1, Histone H2a DioxygenaseDNA-(Apurinic or Apyrimidinic Site) LyaseDNA Transposable Elements

Identifiers

PMID27027282
PMCPMC4977844
OpenAlexW2313190268

What OpenQuestion holds

Textmetadata
LicenceTDM
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.