IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-12126-4.html
   My bibliography  Save this article

TRIM66 reads unmodified H3R2K4 and H3K56ac to respond to DNA damage in embryonic stem cells

Author

Listed:
  • Jiajing Chen

    (University of Science and Technology of China)

  • Zikang Wang

    (Tongji University)

  • Xudong Guo

    (Tongji University)

  • Fudong Li

    (University of Science and Technology of China)

  • Qingtao Wei

    (University of Science and Technology of China)

  • Xuwen Chen

    (University of Science and Technology of China)

  • Deshun Gong

    (Tsinghua University)

  • Yanxin Xu

    (Tongji University)

  • Wen Chen

    (Tongji University)

  • Yongrui Liu

    (University of Science and Technology of China)

  • Jiuhong Kang

    (Tongji University)

  • Yunyu Shi

    (University of Science and Technology of China)

Abstract

Recognition of specific chromatin modifications by distinct structural domains within “reader” proteins plays a critical role in the maintenance of genomic stability. However, the specific mechanisms involved in this process remain unclear. Here we report that the PHD-Bromo tandem domain of tripartite motif-containing 66 (TRIM66) recognizes the unmodified H3R2-H3K4 and acetylated H3K56. The aberrant deletion of Trim66 results in severe DNA damage and genomic instability in embryonic stem cells (ESCs). Moreover, we find that the recognition of histone modification by TRIM66 is critical for DNA damage repair (DDR) in ESCs. TRIM66 recruits Sirt6 to deacetylate H3K56ac, negatively regulating the level of H3K56ac and facilitating the initiation of DDR. Importantly, Trim66-deficient blastocysts also exhibit higher levels of H3K56ac and DNA damage. Collectively, the present findings indicate the vital role of TRIM66 in DDR in ESCs, establishing the relationship between histone readers and maintenance of genomic stability.

Suggested Citation

  • Jiajing Chen & Zikang Wang & Xudong Guo & Fudong Li & Qingtao Wei & Xuwen Chen & Deshun Gong & Yanxin Xu & Wen Chen & Yongrui Liu & Jiuhong Kang & Yunyu Shi, 2019. "TRIM66 reads unmodified H3R2K4 and H3K56ac to respond to DNA damage in embryonic stem cells," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12126-4
    DOI: 10.1038/s41467-019-12126-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-12126-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-12126-4?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
    ---><---

    Citations

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


    Cited by:

    1. Kwangbeom Hyun & Jihye Ahn & Hyoungmin Kim & Jihyun Kim & Yong-In Kim & Hee-Sung Park & Robert G. Roeder & J. Eugene Lee & Jaehoon Kim, 2024. "The BAF complex enhances transcription through interaction with H3K56ac in the histone globular domain," Nature Communications, Nature, vol. 15(1), pages 1-13, 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:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12126-4. 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.