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Genome-wide alteration of 5-hydroxymenthylcytosine in a mouse model of Alzheimer’s disease
- Source :
- BMC Genomics
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Background Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder that leads to a decline in cognitive function. In AD, aggregates of amyloid β peptide precede the accumulation of neurofibrillary tangles, both of which are hallmarks of the disease. The great majority (>90 %) of the AD cases are not originated from genetic defects, therefore supporting the central roles of epigenetic modifications that are acquired progressively during the life span. Strong evidences have indicated the implication of epigenetic modifications, including histone modification and DNA methylation, in AD. Recent studies revealed that 5-hydroxymethylcytosine (5hmC) is dynamically regulated during neurodevelopment and aging. Results We show that amyloid peptide 1–42 (Aβ1-42) could significantly reduce the overall level of 5hmC in vitro. We found that the level of 5hmC displayed differential response to the pathogenesis in different brain regions, including the cortex, cerebellum, and hippocampus of APP-PSEN1 double transgenic (DTg) mice. We observed a significant decrease of overall 5hmC in hippocampus, but not in cortex and cerebellum, as the DTg mice aged. Genome-wide profiling identified differential hydroxymethylation regions (DhMRs) in DTg mice, which are highly enriched in introns, exons and intergenic regions. Gene ontology analyses indicated that DhMR-associated genes are highly enriched in multiple signaling pathways involving neuronal development/differentiation and neuronal function/survival. Conclusions 5hmC-mediated epigenetic regulation could potentially be involved in the pathogenesis of AD. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-2731-1) contains supplementary material, which is available to authorized users.
- Subjects :
- 0301 basic medicine
Amyloid peptide
Aging
Transgene
Mice, Transgenic
Biology
Cell Line
Epigenesis, Genetic
Amyloid beta-Protein Precursor
Mice
03 medical and health sciences
chemistry.chemical_compound
Exon
Alzheimer Disease
Genetics
medicine
Animals
Humans
5-hydroxymethylcytosine
Epigenetics
Gene
5-Hydroxymethylcytosine
Amyloid beta-Peptides
DNA Methylation
medicine.disease
Disease Models, Animal
030104 developmental biology
Histone
chemistry
DNA methylation
DNA demethylation
5-Methylcytosine
biology.protein
Alzheimer's disease
Alzheimer’s disease
Research Article
Genome-Wide Association Study
Biotechnology
Subjects
Details
- ISSN :
- 14712164
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- BMC Genomics
- Accession number :
- edsair.doi.dedup.....42e8a37cc6841e68b3ab21136ab60382