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

Abstract
Data availability
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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

1. Zhou JJ
2. et al
(2022) Histone deacetylase 1 maintains lineage integrity through histone acetylome refinement during early embryogenesis
NCBI Gene Expression Omnibus, GSE198378.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?&acc=GSE198378

The following previously published data sets were used

1. Gupta
2. et al
(2014) Enhancer chromatin signatures predict Smad2/3 binding in Xenopus
NCBI Gene Expression Omnibus, GSE56000.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56000
1. Hontelez
2. et al
(2015) Embryonic transcription is controlled by maternally defined chromatin state
NCBI Gene Expression Omnibus, GSE67974.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE67974
1. Owens
2. et al
(2016) Measuring Absolute RNA Copy Numbers at High Temporal Resolution Reveals Transcriptome Kinetics in Development
NCBI Gene Expression Omnibus, GSE65785.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE65785
1. Charney
2. et al
(2017) Foxh1 marks the embryonic genome prior to the activation of the mesendoderm gene regulatory program
NCBI Gene Expression Omnibus, GSE85273.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE85273
1. Blitz
2. et al
(2017) Regional expression of X. tropicalis transcription factors in early gastrula embryos
NCBI Gene Expression Omnibus, GSE81458.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE81458
1. Tettey
2. et al
(2019) Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
NCBI Gene Expression Omnibus, GSE129236.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE129236

Article and author information

Author details

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.
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.
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.
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.
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.

"This ORCID iD identifies the author of this article:" 0000-0003-4053-5088
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.

"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

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.