1. Developmental Biology
  2. Chromosomes and Gene Expression
Download icon

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
Research Article
  • Cited 67
  • Views 3,300
  • Annotations
Cite this article as: eLife 2016;5:e08851 doi: 10.7554/eLife.08851

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).

Reviewing Editor

  1. Anne C Ferguson-Smith, University of Cambridge, United Kingdom

Publication history

  1. Received: May 21, 2015
  2. Accepted: January 25, 2016
  3. Accepted Manuscript published: February 2, 2016 (version 1)
  4. Version of Record published: April 5, 2016 (version 2)

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.

Metrics

  • 3,300
    Page views
  • 1,243
    Downloads
  • 67
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Developmental Biology
    Meng Zhu et al.
    Research Article

    Apico-basal polarization of cells within the embryo is critical for the segregation of distinct lineages during mammalian development. Polarized cells become the trophectoderm (TE), which forms the placenta, and apolar cells become the inner cell mass (ICM), the founding population of the fetus. The cellular and molecular mechanisms leading to polarization of the human embryo and its timing during embryogenesis have remained unknown. Here, we show that human embryo polarization occurs in two steps: it begins with the apical enrichment of F-actin and is followed by the apical accumulation of the PAR complex. This two-step polarization process leads to the formation of an apical domain at the 8-16 cell stage. Using RNA interference, we show that apical domain formation requires Phospholipase C (PLC) signaling, specifically the enzymes PLCB1 and PLCE1, from the 8-cell stage onwards. Finally, we show that although expression of the critical TE differentiation marker GATA3 can be initiated independently of embryo polarization, downregulation of PLCB1 and PLCE1 decreases GATA3 expression through a reduction in the number of polarized cells. Therefore, apical domain formation reinforces a TE fate. The results we present here demonstrate how polarization is triggered to regulate the first lineage segregation in human embryos.

    1. Developmental Biology
    Eduardo Pulgar et al.
    Research Article Updated

    The developmental strategies used by progenitor cells to allow a safe journey from their induction place towards the site of terminal differentiation are still poorly understood. Here, we uncovered a mechanism of progenitor cell allocation that stems from an incomplete process of epithelial delamination that allows progenitors to coordinate their movement with adjacent extra-embryonic tissues. Progenitors of the zebrafish laterality organ originate from the superficial epithelial enveloping layer by an apical constriction process of cell delamination. During this process, progenitors retain long-lasting apical contacts that enable the epithelial layer to pull a subset of progenitors on their way to the vegetal pole. The remaining delaminated cells follow the movement of apically attached progenitors by a protrusion-dependent cell-cell contact mechanism, avoiding sequestration by the adjacent endoderm, ensuring their collective fate and allocation at the site of differentiation. Thus, we reveal that incomplete delamination serves as a cellular platform for coordinated tissue movements during development.