1. Chromosomes and Gene Expression
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Conversion of random X-inactivation to imprinted X-inactivation by maternal PRC2

  1. Clair Harris
  2. Marissa Cloutier
  3. Megan Trotter
  4. Michael Hinten
  5. Srimonta Gayen
  6. Zhenhai Du
  7. Wei Xie
  8. Sundeep Kalantry  Is a corresponding author
  1. University of Michigan, United States
  2. Tsinghua University, China
Research Article
  • Cited 2
  • Views 1,442
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Cite this article as: eLife 2019;8:e44258 doi: 10.7554/eLife.44258

Abstract

Imprinted X-inactivation silences genes exclusively on the paternally-inherited X-chromosome and is a paradigm of transgenerational epigenetic inheritance in mammals. Here, we test the role of maternal vs. zygotic Polycomb repressive complex 2 (PRC2) protein EED in orchestrating imprinted X-inactivation in mouse embryos. In maternal-null (Eedm-/-) but not zygotic-null (Eed-/-) early embryos, the maternal X-chromosome ectopically induced Xist and underwent inactivation. Eedm-/- females subsequently stochastically silenced Xist from one of the two X-chromosomes and displayed random X-inactivation. This effect was exacerbated in embryos lacking both maternal and zygotic EED (Eedmz-/-), suggesting that zygotic EED can also contribute to the onset of imprinted X-inactivation. Xist expression dynamics in Eedm-/- embryos resemble that of early human embryos, which lack oocyte-derived maternal PRC2 and only undergo random X-inactivation. Thus, expression of PRC2 in the oocyte and transmission of the gene products to the embryo may dictate the occurrence of imprinted X-inactivation in mammals.

Article and author information

Author details

  1. Clair Harris

    Department of Human Genetics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Marissa Cloutier

    Department of Human Genetics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Megan Trotter

    Department of Human Genetics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael Hinten

    Department of Human Genetics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Srimonta Gayen

    Department of Human Genetics, University of Michigan, Ann Arbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Zhenhai Du

    Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Wei Xie

    Center for Stem Cell Biology and Regenerative Medicine, MOE Key Laboratory of Bioinformatics, THU-PKU Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Sundeep Kalantry

    Department of Human Genetics, University of Michigan, Ann Arbor, United States
    For correspondence
    kalantry@umich.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0763-8050

Funding

NIH Office of the Director (DP2-OD-008646)

  • Sundeep Kalantry

National Institutes of Health (R01GM124571)

  • Sundeep Kalantry

National Institutes of Health (R01HD095463)

  • Sundeep Kalantry

National Institute of General Medical Sciences (T32GM07544)

  • Marissa Cloutier
  • Megan Trotter

March of Dimes Foundation (5-FY12-119)

  • Sundeep Kalantry

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All animals were handled according to protocols approved by the University Committee on Use and Care of Animals (UCUCA) at the University of Michigan (protocol #s PRO6455 and PRO8425).

Reviewing Editor

  1. Kavitha Sarma, Wistar Institute, United States

Publication history

  1. Received: December 10, 2018
  2. Accepted: April 1, 2019
  3. Accepted Manuscript published: April 2, 2019 (version 1)
  4. Version of Record published: May 29, 2019 (version 2)

Copyright

© 2019, Harris et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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