IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-04455-7.html
   My bibliography  Save this article

Live-cell single-molecule dynamics of PcG proteins imposed by the DIPG H3.3K27M mutation

Author

Listed:
  • Roubina Tatavosian

    (University of Colorado Denver)

  • Huy Nguyen Duc

    (University of Colorado Denver)

  • Thao Ngoc Huynh

    (University of Colorado Denver)

  • Dong Fang

    (Columbia University)

  • Benjamin Schmitt

    (Colorado State University)

  • Xiaodong Shi

    (Michigan State University)

  • Yiming Deng

    (Michigan State University)

  • Christopher Phiel

    (University of Colorado Denver)

  • Tingting Yao

    (Colorado State University)

  • Zhiguo Zhang

    (Columbia University)

  • Haobin Wang

    (University of Colorado Denver)

  • Xiaojun Ren

    (University of Colorado Denver)

Abstract

Over 80% of diffuse intrinsic pontine gliomas (DIPGs) harbor a point mutation in histone H3.3 where lysine 27 is substituted with methionine (H3.3K27M); however, how the mutation affects kinetics and function of PcG proteins remains elusive. We demonstrate that H3.3K27M prolongs the residence time and search time of Ezh2, but has no effect on its fraction bound to chromatin. In contrast, H3.3K27M has no effect on the residence time of Cbx7, but prolongs its search time and decreases its fraction bound to chromatin. We show that increasing expression of Cbx7 inhibits the proliferation of DIPG cells and prolongs its residence time. Our results highlight that the residence time of PcG proteins directly correlates with their functions and the search time of PcG proteins is critical for regulating their genomic occupancy. Together, our data provide mechanisms in which the cancer-causing histone mutation alters the binding and search dynamics of epigenetic complexes.

Suggested Citation

  • Roubina Tatavosian & Huy Nguyen Duc & Thao Ngoc Huynh & Dong Fang & Benjamin Schmitt & Xiaodong Shi & Yiming Deng & Christopher Phiel & Tingting Yao & Zhiguo Zhang & Haobin Wang & Xiaojun Ren, 2018. "Live-cell single-molecule dynamics of PcG proteins imposed by the DIPG H3.3K27M mutation," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04455-7
    DOI: 10.1038/s41467-018-04455-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-04455-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-04455-7?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
    ---><---

    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:9:y:2018:i:1:d:10.1038_s41467-018-04455-7. 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.