Histone deacetylase 1 maintains lineage integrity through histone acetylome refinement during early embryogenesis

  1. Jeff Jiajing Zhou
  2. Jin Sun Cho
  3. Han Han
  4. Ira L Blitz
  5. Wenqi Wang
  6. Ken WY Cho  Is a corresponding author
  1. University of California, Irvine, United States

Abstract

Histone acetylation is a pivotal epigenetic modification that controls chromatin structure and regulates gene expression. It plays an essential role in modulating zygotic transcription and cell lineage specification of developing embryos. While the outcomes of many inductive signals have been described to require enzymatic activities of histone acetyltransferases and deacetylases (HDACs), the mechanisms by which HDACs confine the utilization of the zygotic genome remain to be elucidated. Here, we show that histone deacetylase 1 (Hdac1) progressively binds to the zygotic genome from mid blastula and onward. The recruitment of Hdac1 to the genome at blastula is instructed maternally. Cis-regulatory modules (CRMs) bound by Hdac1 possess epigenetic signatures underlying distinct functions. We highlight a dual function model of Hdac1 where Hdac1 not only represses gene expression by sustaining a histone hypoacetylation state on inactive chromatin, but also maintains gene expression through participating in dynamic histone acetylation-deacetylation cycles on active chromatin. As a result, Hdac1 maintains differential histone acetylation states of bound CRMs between different germ layers and reinforces the transcriptional program underlying cell lineage identities, both in time and space. Taken together, our study reveals a comprehensive role for Hdac1 during early vertebrate embryogenesis.

Data availability

Sequencing data have been deposited in GEO under accession code GSE198378.Publicly available datasets used in this study are available at NCBI Gene Expression Omnibus using the accession GSE56000, GSE67974 ,GSE65785, GSE85273, GSE81458, GSE129236. Relevant bioinformatic analysis scripts are accessible at https://github.com/jiajinglz/bioRxiv_05052022_Hdac_dual_roles.

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

Article and author information

Author details

  1. Jeff Jiajing Zhou

    Department of Developmental and Cell Biology, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Jin Sun Cho

    Department of Developmental and Cell Biology, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Han Han

    Department of Developmental and Cell Biology, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ira L Blitz

    Department of Developmental and Cell Biology, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Wenqi Wang

    Department of Developmental and Cell Biology, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4053-5088
  6. Ken WY Cho

    Department of Developmental and Cell Biology, University of California, Irvine, Irvine, United States
    For correspondence
    kwcho@uci.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7282-1770

Funding

National Institute of General Medical Sciences (R01GM126395)

  • Ken WY Cho

National Institute of General Medical Sciences (R35GM139617)

  • Ken WY Cho

National Science Foundation (1755214)

  • Ken WY Cho

National Institute of General Medical Sciences (R01GM126048)

  • Wenqi Wang

American Cancer Society (RSG-18-009-01-CCG)

  • Wenqi Wang

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 the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#AUP-21-068) of the University of California, Irvine.

Copyright

© 2023, Zhou 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. Jeff Jiajing Zhou
  2. Jin Sun Cho
  3. Han Han
  4. Ira L Blitz
  5. Wenqi Wang
  6. Ken WY Cho
(2023)
Histone deacetylase 1 maintains lineage integrity through histone acetylome refinement during early embryogenesis
eLife 12:e79380.
https://doi.org/10.7554/eLife.79380

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https://doi.org/10.7554/eLife.79380

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