Histone deacetylase 1 maintains lineage integrity through histone acetylome refinement during early embryogenesis
- 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.
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Enhancer chromatin signatures predict Smad2/3 binding in XenopusNCBI Gene Expression Omnibus, GSE56000.
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Embryonic transcription is controlled by maternally defined chromatin stateNCBI Gene Expression Omnibus, GSE67974.
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Foxh1 marks the embryonic genome prior to the activation of the mesendoderm gene regulatory programNCBI Gene Expression Omnibus, GSE85273.
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Regional expression of X. tropicalis transcription factors in early gastrula embryosNCBI Gene Expression Omnibus, GSE81458.
Article and author information
Author details
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.
Reviewing Editor
- Matthew C. Good, University of Pennsylvania Perelman School of Medicine, United States
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.
Version history
- Received: April 9, 2022
- Preprint posted: May 6, 2022 (view preprint)
- Accepted: March 24, 2023
- Accepted Manuscript published: March 27, 2023 (version 1)
- Version of Record published: April 6, 2023 (version 2)
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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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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