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

Jeff Jiajing Zhou, Jin Sun Cho, Han Han, View ORCID ProfileIra L. Blitz, View ORCID ProfileWenqi Wang, View ORCID ProfileKen W.Y. Cho
doi: https://doi.org/10.1101/2022.05.05.490762
Jeff Jiajing Zhou
1Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA
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Jin Sun Cho
1Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA
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Han Han
1Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA
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Ira L. Blitz
1Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA
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Wenqi Wang
1Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA
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Ken W.Y. Cho
1Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA
2Center for Complex Biological Systems, University of California, Irvine, CA, USA
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  • For correspondence: kwcho@uci.edu
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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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 06, 2022.
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Histone deacetylase 1 maintains lineage integrity through histone acetylome refinement during early embryogenesis
Jeff Jiajing Zhou, Jin Sun Cho, Han Han, Ira L. Blitz, Wenqi Wang, Ken W.Y. Cho
bioRxiv 2022.05.05.490762; doi: https://doi.org/10.1101/2022.05.05.490762
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Histone deacetylase 1 maintains lineage integrity through histone acetylome refinement during early embryogenesis
Jeff Jiajing Zhou, Jin Sun Cho, Han Han, Ira L. Blitz, Wenqi Wang, Ken W.Y. Cho
bioRxiv 2022.05.05.490762; doi: https://doi.org/10.1101/2022.05.05.490762

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