Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation

  1. Katia Ancelin
  2. Laurène Syx
  3. Maud Borensztein
  4. Noémie Ranisavljevic
  5. Ivaylo Vassilev
  6. Luis Briseño-Roa
  7. Tao Liu
  8. Eric Metzger
  9. Nicolas Servant
  10. Emmanuel Barillot
  11. Chong-Jian Chen
  12. Roland Schüle
  13. Edith Heard  Is a corresponding author
  1. Institut Curie, France
  2. High Fidelity Biology, France
  3. Annoroad Gene Technology Co., Ltd, China
  4. Urologische Klinik und Zentrale Klinische Forschung, Germany

Abstract

Upon fertilization, the highly specialised sperm and oocyte genomes are remodelled to confer totipotency. The mechanisms of the dramatic reprogramming events that occur have remained unknown, and presumed roles of histone modifying enzymes are just starting to be elucidated. Here, we explore the function of the oocyte-inherited pool of a histone H3K4 and K9 demethylase, LSD1/KDM1A during early mouse development. KDM1A deficiency results in developmental arrest by the two-cell stage, accompanied by dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns. At the transcriptional level, the switch of the maternal-to-zygotic transition fails to be induced properly and LINE-1 retrotransposons are not properly silenced. We propose that KDM1A plays critical roles in establishing the correct epigenetic landscape of the zygote upon fertilization, in preserving genome integrity and in initiating new patterns of genome expression that drive early mouse development.

Article and author information

Author details

  1. Katia Ancelin

    Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Laurène Syx

    Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Maud Borensztein

    Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Noémie Ranisavljevic

    Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Ivaylo Vassilev

    Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Luis Briseño-Roa

    High Fidelity Biology, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Tao Liu

    Annoroad Gene Technology Co., Ltd, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Eric Metzger

    Urologische Klinik und Zentrale Klinische Forschung, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Nicolas Servant

    Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Emmanuel Barillot

    Institut Curie, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Chong-Jian Chen

    Annoroad Gene Technology Co., Ltd, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Roland Schüle

    Urologische Klinik und Zentrale Klinische Forschung, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  13. Edith Heard

    Institut Curie, Paris, France
    For correspondence
    Edith.Heard@curie.fr
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All mice used were handled with care and according to approved institutional animal care and use committee of the Institut Curie (CEEA-IC) protocols(C 75-05-18). The work has also been conducted under the approval from the French Ministry of Higher Education and Research for the use of Genetically Modified Organisms (agreement number 5549CA-I).

Copyright

© 2016, Ancelin 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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https://doi.org/10.7554/eLife.08851

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