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A genome‐wide profiling of brain DNA hydroxymethylation in Alzheimer's disease
Author(s) -
Zhao Jinying,
Zhu Yun,
Yang Jingyun,
Li Lin,
Wu Hao,
De Jager Philip L.,
Jin Peng,
Bennett David A.
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.10.004
Subject(s) - dna methylation , epigenetics , biology , 5 hydroxymethylcytosine , genome , dna demethylation , gene , human genome , dna , alzheimer's disease , computational biology , genetics , disease , gene expression , medicine , pathology
Abstract Introduction DNA methylation is a key epigenetic mechanism in brain aging and Alzheimer's disease (AD). The newly discovered 5‐hydroxymethylcytosine mediates DNA demethylation, is highly abundant in the brain, and is dynamically regulated by life experiences. However, little is known about its genome‐wide patterns and potential role in AD. Methods Using a genome‐wide capture followed by high‐throughput sequencing, we studied the genome‐wide distribution of 5‐hydroxymethylcytosine at specific genomic loci in human AD brain and identified differentially hydroxymethylated regions (DhMRs) associated with AD pathology. Results We identified 517 DhMRs significantly associated with neuritic plaques and 60 DhMRs associated with neurofibrillary tangles. DNA hydroxymethylation in gene bodies was predominantly positively correlated with cis ‐acting gene expression. Moreover, genes showing differential hydroxymethylation were significantly enriched in neurobiological processes and clustered in functional gene ontology categories. Discussion Our results reveal a critical role of DNA hydroxymethylation in AD pathology and provide mechanistic insight into the molecular mechanisms underlying AD.