Histone acetylation homeodynamics navigates cell survival and apoptosis
Abstract
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.
Article Details
Authors (13)
Kang Li
Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University
Ling Tian
Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding/Guangdong Provincial Sericulture and Mulberry Engineering Research Center, College of Animal Science, South China Agricultural University
Wenxin Cao
Jiahui Zhang
Department of Radiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University
Wenhao Zhang
School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai 201210, China
Tong Lin
Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University
Shumin Huang
Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University
Yongyu Qiu
Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University
Zifeng Ruan
Jianhao Deng
Shihui Long
Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University
Subba R. Palli
Department of Entomology, College of Agriculture, Food, and Environment, University of Kentucky
Sheng Li