Establishment of developmental gene silencing by ordered polycomb complex recruitment in early zebrafish embryos

  1. Graham JM Hickey
  2. Candice L Wike
  3. Xichen Nie
  4. Yixuan Guo
  5. Mengyao Tan
  6. Patrick J Murphy
  7. Bradley R Cairns  Is a corresponding author
  1. Howard Hughes Medical Institute, University of Utah School of Medicine, United States

Abstract

Vertebrate embryos achieve developmental competency during zygotic genome activation (ZGA) by establishing chromatin states that silence yet poise developmental genes for subsequent lineage-specific activation. Here, we reveal the order of chromatin states in establishing developmental gene poising in preZGA zebrafish embryos. Poising is established at promoters and enhancers that initially contain open/permissive chromatin with 'Placeholder' nucleosomes (bearing H2A.Z, H3K4me1, and H3K27ac), and DNA hypomethylation. Silencing is initiated by the recruitment of Polycomb Repressive Complex 1 (PRC1), and H2Aub1 deposition by catalytic Rnf2 during preZGA and ZGA stages. During postZGA, H2Aub1 enables Aebp2-containing PRC2 recruitment and H3K27me3 deposition. Notably, preventing H2Aub1 (via Rnf2 inhibition) eliminates recruitment of Aebp2-PRC2 and H3K27me3, and elicits transcriptional upregulation of certain developmental genes during ZGA. However, upregulation is independent of H3K27me3 - establishing H2Aub1 as the critical silencing modification at ZGA. Taken together, we reveal the logic and mechanism for establishing poised/silent developmental genes in early vertebrate embryos.

Data availability

Sequencing data have been deposited in GEO under accession code GSE168362.

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

Article and author information

Author details

  1. Graham JM Hickey

    Department of Oncological Sciences, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Candice L Wike

    Department of Oncological Sciences, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Xichen Nie

    Department of Oncological Sciences, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yixuan Guo

    Department of Oncological Sciences, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1940-1931
  5. Mengyao Tan

    Department of Oncological Sciences, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Patrick J Murphy

    Department of Oncological Sciences, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Bradley R Cairns

    Department of Oncological Sciences, Howard Hughes Medical Institute, University of Utah School of Medicine, Salt Lake City, United States
    For correspondence
    brad.cairns@hci.utah.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9864-8811

Funding

Howard Hughes Medical Institute (Cairns)

  • Bradley R Cairns

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

Ethics

Animal experimentation: All of our work on zebrafish is authorized and overseen by our institutional animal care and use committee (IACUC). This work is authorized by the current IACUC Protocol #IACUC protocol 20-04011 'Germ Cell Epigenetics in Zebrafish'. We have no surgical procedures, and followed AVMA Guidelines involving a 2-step euthanasia for embryos and larvae which includes rapid chilling followed by immersion in a dilute sodium hypochlorite solution (discussed on page 89 of the 2020 Guidelines).

Copyright

© 2022, Hickey 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. Graham JM Hickey
  2. Candice L Wike
  3. Xichen Nie
  4. Yixuan Guo
  5. Mengyao Tan
  6. Patrick J Murphy
  7. Bradley R Cairns
(2022)
Establishment of developmental gene silencing by ordered polycomb complex recruitment in early zebrafish embryos
eLife 11:e67738.
https://doi.org/10.7554/eLife.67738

Share this article

https://doi.org/10.7554/eLife.67738

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