Lee, Min Young Lee, Junghee Hyeon, Seung Jae Cho, Hyesun Hwang, Yu Jin Shin, Jong-Yeon McKee, Ann C. Kowall, Neil W. Kim, Jong-Il Stein, Thor D. Hwang, Daehee Ryu, Hoon 2024-01-19T17:31:40Z 2024-01-19T17:31:40Z 2021-09-05 2020-06 1474-9718 https://pubs.kist.re.kr/handle/201004/118569 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 H3K9me3-mediated heterochromatin condensation is elevated in the cortex of sporadic AD postmortem brains. In order to identify which epigenomes are modulated by heterochromatin, we performed H3K9me3-chromatin immunoprecipitation (ChIP)-sequencing and mRNA-sequencing on postmortem brains from normal subjects and AD patients. The integrated analyses of genome-wide ChIP- and mRNA-sequencing data identified epigenomes that were highly occupied by H3K9me3 and inversely correlated with their mRNA expression levels in AD. Biological network analysis further revealed H3K9me3-landscaped 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 down-regulation of synaptic function-related genes, suggesting that the epigenetic alteration by H3K9me3 is associated with the synaptic pathology of sporadic AD. English WILEY EPIGENETIC MECHANISMS EXPRESSION ANALYSIS BETA DEPOSITION GENE-EXPRESSION MOUSE MODEL BRAIN PROTEIN NEURODEGENERATION HETEROCHROMATIN DEMENTIA Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease Article 10.1111/acel.13153 1 AGING CELL, v.19, no.6 AGING CELL 19 6 scie scopus 000533224600001 2-s2.0-85085010835 Cell Biology Geriatrics & Gerontology Cell Biology Geriatrics & Gerontology Article EPIGENETIC MECHANISMS EXPRESSION ANALYSIS BETA DEPOSITION GENE-EXPRESSION MOUSE MODEL BRAIN PROTEIN NEURODEGENERATION HETEROCHROMATIN DEMENTIA Alzheimer&apos s disease epigenetic modifications genome-wide sequencing synaptic transmission