Intergenerational epigenetic inheritance mediated by MYS-2/MOF in the pathogenesis of Alzheimer’s disease
Yuhong Li,
Hua Bai,
Wenwen Liu,
Wenhui Zhou,
Huan Gu,
Peiji Zhao,
Man Zhu,
Yixin Li,
Xinyi Yan,
Ninghui Zhao,
Xiaowei Huang
Affiliations
Yuhong Li
School of Medicine, State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China; College of Biological Resources and Food Engineering, Qujing Normal University, Qujing 655000, China
Hua Bai
School of Medicine, State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China; School of Public Health, Kunming Medical University, Kunming 650500, China
Wenwen Liu
School of Medicine, State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China
Wenhui Zhou
School of Medicine, State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China
Huan Gu
School of Medicine, State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China
Peiji Zhao
School of Medicine, State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China
Man Zhu
School of Medicine, State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China; College of Biological Resources and Food Engineering, Qujing Normal University, Qujing 655000, China
Yixin Li
School of Medicine, State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China
Xinyi Yan
School of Medicine, State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China
Ninghui Zhao
Neurosurgery of the Second Hospital Affiliated with Kunming Medical University, Kunming 650101, China; Corresponding author
Xiaowei Huang
School of Medicine, State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming 650091, China; Corresponding author
Summary: Although autosomal-dominant inheritance is believed an important cause of familial clustering Alzheimer’s disease (FAD), it covers only a small proportion of FAD incidence, and so we investigated epigenetic memory as an alternative mechanism to contribute for intergenerational AD pathogenesis. Our data in vivo showed that mys-2 of Caenorhabditis elegans that encodes a putative MYST acetyltransferase responsible for H4K16 acetylation modulated AD occurrence. The phenotypic improvements in the parent generation caused by mys-2 disfunction were passed to their progeny due to epigenetic memory, which resulted in similar H4K16ac levels among the candidate target genes of MYS-2 and similar gene expression patterns of the AD-related pathways. Furthermore, the ROS/CDK-5/ATM pathway functioned as an upstream activator of MYS-2. Our study indicated that MYS-2/MOF could be inherited intergenerationally via epigenetic mechanisms in C. elegans and mammalian cell of AD model, providing a new insight into our understanding of the etiology and inheritance of FAD.
