Dynamic enhancer partitioning instructs activation of a growth-related gene during exit from naïve pluripotency

  1. Maxim Van Cleef Greenberg  Is a corresponding author
  2. Aurélie Teissandier
  3. Marius Walter
  4. Daan Noordermeer
  5. Deborah Bourc'his  Is a corresponding author
  1. Institut Curie, France
  2. The Buck Institute for Research on Aging, United States
  3. Université Paris-Saclay, France

Abstract

During early mammalian development, the chromatin landscape undergoes profound transitions. The Zdbf2 gene-involved in growth control-provides a valuable model to study this window: upon exit from naïve pluripotency and prior to tissue differentiation, it undergoes a switch from a distal to a proximal promoter usage, accompanied by a switch from polycomb to DNA methylation occupancy. Using an embryonic stem cell (ESC) system to mimic this period, we show here that four enhancers contribute to the Zdbf2 promoter switch, concomitantly with dynamic changes in chromatin architecture. In ESCs, the locus is partitioned to facilitate enhancer contacts with the distal Zdbf2 promoter. Relieving the partition enhances proximal Zdbf2 promoter activity, as observed during differentiation or with genetic mutants. Importantly, we show that 3D regulation occurs upstream of the polycomb and DNA methylation pathways. Our study reveals the importance of multi-layered regulatory frameworks to ensure proper spatio-temporal activation of developmentally important genes.

Data availability

Sequencing data have been deposited in GEO under accession code GSE121405.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Maxim Van Cleef Greenberg

    Unité de Génétique et Biologie du Développement, Institut Curie, Paris, France
    For correspondence
    maxim.greenberg@curie.fr
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9935-8763
  2. Aurélie Teissandier

    Department of Genetics and Developmental Biology, Institut Curie, Paris, France
    Competing interests
    No competing interests declared.
  3. Marius Walter

    The Buck Institute for Research on Aging, Novato, United States
    Competing interests
    No competing interests declared.
  4. Daan Noordermeer

    Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, Gif sur Yvette, France
    Competing interests
    No competing interests declared.
  5. Deborah Bourc'his

    Unité de Génétique et Biologie du Développement, Institut Curie, Paris, France
    For correspondence
    Deborah.Bourchis@curie.fr
    Competing interests
    Deborah Bourc'his, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9499-7291

Funding

H2020 European Research Council (Cog EpiRepro)

  • Deborah Bourc'his

European Molecular Biology Organization (LTF 457-2013)

  • Maxim Van Cleef Greenberg

Fondation ARC pour la Recherche sur le Cancer (Post-doc Fellowship)

  • Maxim Van Cleef Greenberg

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

Copyright

© 2019, Greenberg 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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  1. Maxim Van Cleef Greenberg
  2. Aurélie Teissandier
  3. Marius Walter
  4. Daan Noordermeer
  5. Deborah Bourc'his
(2019)
Dynamic enhancer partitioning instructs activation of a growth-related gene during exit from naïve pluripotency
eLife 8:e44057.
https://doi.org/10.7554/eLife.44057

Share this article

https://doi.org/10.7554/eLife.44057

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