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- W3024012994 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." @default.
- W3024012994 created "2020-05-21" @default.
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- W3024012994 date "2020-05-17" @default.
- W3024012994 modified "2023-10-17" @default.
- W3024012994 title "Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease" @default.
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- W3024012994 doi "https://doi.org/10.1111/acel.13153" @default.
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