Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease
- Epigenome signatures landscaped by histone H3K9me3 are associated with the synaptic dysfunction in Alzheimer's disease
- 류훈; 현승재; Min Young Lee; Junghee Lee; 조혜선; 황유진; Jong-Yeon Shin; Ann C. McKee; Neil W. Kowall; Jong-Il Kim; Thor D Stein; 황대희
- Issue Date
- Aging cell
- VOL 19, NO 6, e13153
- 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.
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