期刊
CLINICAL EPIGENETICS
卷 11, 期 -, 页码 -出版社
BMC
DOI: 10.1186/s13148-019-0672-7
关键词
DNA methylation; Alzheimer's; Hippocampus; Adult neurogenesis; Poised promoters; Homeobox; Neurodevelopment; Epigenetics
资金
- Spanish Government through Institute of Health Carlos III [FIS PI13/02730, PI17/02218]
- European Regional Development Fund (ERDF)
- European Union
- Regional Basque Government through Basque Foundation for Health Innovation and Research (BIOEF) [BIO12/ALZ/007]
- Fundacion Caja-Navarra
- Trans-Pyrenean Biomedical Research Network (REFBIO)
- PRECIPITA platform (Spanish foundation for science and technology-FECYT)
- LaCaixa Foundation
- Fundacion Bancaria la Caixa
BackgroundDrawing the epigenome landscape of Alzheimer's disease (AD) still remains a challenge. To characterize the epigenetic molecular basis of the human hippocampus in AD, we profiled genome-wide DNA methylation levels in hippocampal samples from a cohort of pure AD patients and controls by using the Illumina 450K methylation arrays.ResultsUp to 118 AD-related differentially methylated positions (DMPs) were identified in the AD hippocampus, and extended mapping of specific regions was obtained by bisulfite cloning sequencing. AD-related DMPs were significantly correlated with phosphorylated tau burden. Functional analysis highlighted that AD-related DMPs were enriched in poised promoters that were not generally maintained in committed neural progenitor cells, as shown by ChiP-qPCR experiments. Interestingly, AD-related DMPs preferentially involved neurodevelopmental and neurogenesis-related genes. Finally, InterPro ontology analysis revealed enrichment in homeobox-containing transcription factors in the set of AD-related DMPs.ConclusionsThese results suggest that altered DNA methylation in the AD hippocampus occurs at specific regulatory regions crucial for neural differentiation supporting the notion that adult hippocampal neurogenesis may play a role in AD through epigenetic mechanisms.
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