Histone acetylation homeodynamics navigates cell survival and apoptosis

Kang Li; Ling Tian; Wenxin Cao; Jiahui Zhang; Wenhao Zhang; Tong Lin; Shumin Huang; Yongyu Qiu; Zifeng Ruan; Jianhao Deng; Shihui Long; Subba R. Palli; Sheng Li

doi:10.1038/s41467-025-66405-4

Histone acetylation homeodynamics navigates cell survival and apoptosis

Kang Li
, Ling Tian
, Wenxin Cao
, Jiahui Zhang
, Wenhao Zhang
, Tong Lin
, Shumin Huang
, Yongyu Qiu
, Zifeng Ruan
, Jianhao Deng
, Shihui Long
, Subba R. Palli
, Sheng Li

Research output: Contribution to journal › Article › peer-review

Abstract

The balance between inhibitor of apoptosis proteins (IAPs) and pro-apoptotic proteins (PAPs) tightly and precisely regulates cellular homeostasis. However, the epigenetic mechanism by which this balance is maintained in vivo remains largely unknown. Here we show that in various Drosophila tissues, the homeodynamics of H3K14ac/H3K27ac/H4K8ac on the promoters/enhancers of E93 and PAPs (rpr/hid), modulated by P300-CtBP/HDAC3, directs the decision between cell survival and the activation of hormone-induced developmental apoptosis. Concurrently, the homeodynamics of H3K14ac/H3K27ac/H4K8ac in IAPs (Diap1) promoters, modulated by Tip60/P300-CtBP/HDAC3, sustains cellular homeostasis by antagonizing the activities of PAPs. Notably, the epigenetic mechanism revealed in Drosophila is partially conserved in mammals. Moreover, disrupting the histone acetylation homeodynamics attenuates tumorigenesis through altering the balances between IAPs and PAPs in Drosophila and mice. In conclusion, histone acetylation homeodynamics navigates cell survival and apoptosis, suggesting potential epigenetic targets for the treatment of diseases or tumors caused by the imbalance between IAPs and PAPs.

Original language	English
Article number	11358
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-66405-4
State	Published - Dec 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Funding

We thank Dr. Zizhang Zhou (Shandong Agricultural University) for providing fly stocks and figraw for providing the material for the images. This study was supported by the National Natural Science Foundation of China (32220103003 to S.L. and 32070491 to K.L.), the Department of Science and Technology of Guangdong Province (grant 2019B090905003 to S.L.), and the Natural Science Foundation of Guangdong Province (2024A1515013140 to K.L.). English was polished by the Nature Publishing Group.

Funders	Funder number
Shandong Agricultural University
Nature Publishing Group
National Natural Science Foundation of China (NSFC)	32220103003, 32070491
Guangdong Provincial Department of Science and Technology and Guangzhou Science Technology and Innovation Commission	2019B090905003
Natural Science Foundation of Guangdong Province	2024A1515013140

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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10.1038/s41467-025-66405-4

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title = "Histone acetylation homeodynamics navigates cell survival and apoptosis",

abstract = "The balance between inhibitor of apoptosis proteins (IAPs) and pro-apoptotic proteins (PAPs) tightly and precisely regulates cellular homeostasis. However, the epigenetic mechanism by which this balance is maintained in vivo remains largely unknown. Here we show that in various Drosophila tissues, the homeodynamics of H3K14ac/H3K27ac/H4K8ac on the promoters/enhancers of E93 and PAPs (rpr/hid), modulated by P300-CtBP/HDAC3, directs the decision between cell survival and the activation of hormone-induced developmental apoptosis. Concurrently, the homeodynamics of H3K14ac/H3K27ac/H4K8ac in IAPs (Diap1) promoters, modulated by Tip60/P300-CtBP/HDAC3, sustains cellular homeostasis by antagonizing the activities of PAPs. Notably, the epigenetic mechanism revealed in Drosophila is partially conserved in mammals. Moreover, disrupting the histone acetylation homeodynamics attenuates tumorigenesis through altering the balances between IAPs and PAPs in Drosophila and mice. In conclusion, histone acetylation homeodynamics navigates cell survival and apoptosis, suggesting potential epigenetic targets for the treatment of diseases or tumors caused by the imbalance between IAPs and PAPs.",

author = "Kang Li and Ling Tian and Wenxin Cao and Jiahui Zhang and Wenhao Zhang and Tong Lin and Shumin Huang and Yongyu Qiu and Zifeng Ruan and Jianhao Deng and Shihui Long and Palli, \{Subba R.\} and Sheng Li",

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AU - Qiu, Yongyu

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Histone acetylation homeodynamics navigates cell survival and apoptosis

Abstract

Bibliographical note

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