IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v532y2016i7599d10.1038_nature17640.html
   My bibliography  Save this article

DNA methylation on N6-adenine in mammalian embryonic stem cells

Author

Listed:
  • Tao P. Wu

    (Yale School of Medicine)

  • Tao Wang

    (Yale School of Medicine)

  • Matthew G. Seetin

    (Pacific Biosciences)

  • Yongquan Lai

    (Environmental Sciences & Engineering, University of North Carolina at Chapel Hill)

  • Shijia Zhu

    (Icahn School of Medicine at Mount Sinai)

  • Kaixuan Lin

    (Yale School of Medicine)

  • Yifei Liu

    (Yale School of Medicine)

  • Stephanie D. Byrum

    (University of Arkansas for Medical Sciences, Little Rock)

  • Samuel G. Mackintosh

    (University of Arkansas for Medical Sciences, Little Rock)

  • Mei Zhong

    (Yale School of Medicine)

  • Alan Tackett

    (University of Arkansas for Medical Sciences, Little Rock)

  • Guilin Wang

    (Yale Center for Genome Analysis, Yale School of Medicine)

  • Lawrence S. Hon

    (Pacific Biosciences)

  • Gang Fang

    (Icahn School of Medicine at Mount Sinai)

  • James A. Swenberg

    (Environmental Sciences & Engineering, University of North Carolina at Chapel Hill)

  • Andrew Z. Xiao

    (Yale School of Medicine)

Abstract

It has been widely accepted that 5-methylcytosine is the only form of DNA methylation in mammalian genomes. Here we identify N6-methyladenine as another form of DNA modification in mouse embryonic stem cells. Alkbh1 encodes a demethylase for N6-methyladenine. An increase of N6-methyladenine levels in Alkbh1-deficient cells leads to transcriptional silencing. N6-methyladenine deposition is inversely correlated with the evolutionary age of LINE-1 transposons; its deposition is strongly enriched at young ( 6 million years old) L1 elements. The deposition of N6-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, N6-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 N6-methyladenine constitutes a crucial component of the epigenetic regulation repertoire in mammalian genomes.

Suggested Citation

  • Tao P. Wu & Tao Wang & Matthew G. Seetin & Yongquan Lai & Shijia Zhu & Kaixuan Lin & Yifei Liu & Stephanie D. Byrum & Samuel G. Mackintosh & Mei Zhong & Alan Tackett & Guilin Wang & Lawrence S. Hon & , 2016. "DNA methylation on N6-adenine in mammalian embryonic stem cells," Nature, Nature, vol. 532(7599), pages 329-333, April.
    • Handle: RePEc:nat:nature:v:532:y:2016:i:7599:d:10.1038_nature17640
    DOI: 10.1038/nature17640
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature17640
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature17640?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Ádám Sturm & Éva Saskői & Bernadette Hotzi & Anna Tarnóci & János Barna & Ferenc Bodnár & Himani Sharma & Tibor Kovács & Eszter Ari & Nóra Weinhardt & Csaba Kerepesi & András Perczel & Zoltán Ivics & , 2023. "Downregulation of transposable elements extends lifespan in Caenorhabditis elegans," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Jiyun Chen & Rong Hu & Ying Chen & Xiaofeng Lin & Wenwen Xiang & Hong Chen & Canglin Yao & Liang Liu, 2022. "Structural basis for MTA1c-mediated DNA N6-adenine methylation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:532:y:2016:i:7599:d:10.1038_nature17640. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.