Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease.
Aging Cell
; 19(6): e13153, 2020 06.
Article
em En
| MEDLINE
| ID: mdl-32419307
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 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Histonas
/
Transmissão Sináptica
/
Doença de Alzheimer
/
Epigenoma
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Aging Cell
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos