IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms4818.html
   My bibliography  Save this article

The histone H2A deubiquitinase Usp16 regulates embryonic stem cell gene expression and lineage commitment

Author

Listed:
  • Wei Yang

    (Stem Cell Institute, University of Alabama at Birmingham)

  • Yun-Hwa Lee

    (Yong Loo Lin School of Medicine, National University of Singapore)

  • Amanda E. Jones

    (Stem Cell Institute, University of Alabama at Birmingham)

  • Jessica L. Woolnough

    (Stem Cell Institute, University of Alabama at Birmingham)

  • Dewang Zhou

    (Stem Cell Institute, University of Alabama at Birmingham)

  • Qian Dai

    (University of Alabama at Birmingham, West Pavilion)

  • Qiang Wu

    (Yong Loo Lin School of Medicine, National University of Singapore)

  • Keith E. Giles

    (Stem Cell Institute, University of Alabama at Birmingham)

  • Tim M. Townes

    (Stem Cell Institute, University of Alabama at Birmingham)

  • Hengbin Wang

    (Stem Cell Institute, University of Alabama at Birmingham)

Abstract

Polycomb Repressive Complex 1 and histone H2A ubiquitination (ubH2A) contribute to embryonic stem cell (ESC) pluripotency by repressing lineage-specific gene expression. However, whether active deubiquitination co-regulates ubH2A levels in ESCs and during differentiation is not known. Here we report that Usp16, a histone H2A deubiquitinase, regulates H2A deubiquitination and gene expression in ESCs, and importantly, is required for ESC differentiation. Usp16 knockout is embryonic lethal in mice, but does not affect ESC viability or identity. Usp16 binds to the promoter regions of a large number of genes in ESCs, and Usp16 binding is inversely correlated with ubH2A levels, and positively correlates with gene expression levels. Intriguingly, Usp16−/− ESCs fail to differentiate due to ubH2A-mediated repression of lineage-specific genes. Finally, Usp16, but not a catalytically inactive mutant, rescues the differentiation defects of Usp16−/− ESCs. Therefore, this study identifies Usp16 and H2A deubiquitination as critical regulators of ESC gene expression and differentiation.

Suggested Citation

  • Wei Yang & Yun-Hwa Lee & Amanda E. Jones & Jessica L. Woolnough & Dewang Zhou & Qian Dai & Qiang Wu & Keith E. Giles & Tim M. Townes & Hengbin Wang, 2014. "The histone H2A deubiquitinase Usp16 regulates embryonic stem cell gene expression and lineage commitment," Nature Communications, Nature, vol. 5(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4818
    DOI: 10.1038/ncomms4818
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms4818
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms4818?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. Gaozan Tong & Yiming Chen & Xixi Chen & Junfu Fan & Kunxuan Zhu & ZiJing Hu & Santie Li & Junjie Zhu & Jianjun Feng & Zhaohang Wu & Zhenyu Hu & Bin Zhou & Litai Jin & Hui Chen & Jingling Shen & Weitao, 2023. "FGF18 alleviates hepatic ischemia-reperfusion injury via the USP16-mediated KEAP1/Nrf2 signaling pathway in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Julian Cheron & Leonardo Beccari & Perrine Hagué & Romain Icick & Chloé Despontin & Teresa Carusone & Matthieu Defrance & Sagar Bhogaraju & Elena Martin-Garcia & Roberto Capellan & Rafael Maldonado & , 2023. "USP7/Maged1-mediated H2A monoubiquitination in the paraventricular thalamus: an epigenetic mechanism involved in cocaine use disorder," Nature Communications, Nature, vol. 14(1), pages 1-18, 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:5:y:2014:i:1:d:10.1038_ncomms4818. 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.