Histone acetylation homeodynamics navigates cell survival and apoptosis

作者：Kang Li, Ling Tian, Wenxin Cao, Jiahui Zhang, Wenhao Zhang, Lin Tong, Shu‐Min Huang, Yongyu Qiu, Zifeng Ruan, Jianhao Deng, Shihui Long, Subba Reddy Palli, Sheng Li · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-66405-4 · 被引用次数：4 · 研究领域：Histone Deacetylase Inhibitors Research、Genomics and Chromatin Dynamics、Ubiquitin and proteasome pathways

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.