Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease

Title
Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease
Authors
류훈현승재Min Young LeeJunghee Lee조혜선황유진Jong-Yeon ShinAnn C. McKeeNeil W. KowallJong-Il KimThor D Stein황대희
Issue Date
2020-06
Publisher
Aging cell
Citation
VOL 19, NO 6, e13153
Abstract
The pathogenesis of Alzheimer's disease (AD) and the commonest cause of dementia in the elderly remain incompletely understood. Recently, epigenetic modifications have been shown to play a potential role in neurodegeneration, but the specific involvement of epigenetic signatures landscaped by heterochromatin has not been studied in AD. Herein, we discovered that H3K9me3­mediated heterochromatin condensation is elevated in the cortex of sporadic AD postmortem brains. In order to identify which epigenomes are modulated by heterochromatin, we performed H3K9me3­chromatin immunoprecipitation (ChIP)­sequencing and mRNA­sequencing on postmortem brains from normal subjects and AD patients. The integrated analyses of genome­wide ChIP­ and mRNA­sequencing data identified epigenomes that were highly occupied by H3K9me3 and inversely correlated with their mRNA expression levels in AD. Biological network analysis further revealed H3K9me3­landscaped epigenomes to be mainly involved in synaptic transmission, neuronal differentiation, and cell motility. Together, our data show that the abnormal heterochromatin remodeling by H3K9me3 leads to down­regulation of synaptic function­related genes, suggesting that the epigenetic alteration by H3K9me3 is associated with the synaptic pathology of sporadic AD.
URI
http://pubs.kist.re.kr/handle/201004/72325
ISSN
1474-9718
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KIST Publication > Article
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