Journal
BMC GENOMICS
Volume 17, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s12864-016-2731-1
Keywords
Alzheimer's disease; 5-hydroxymethylcytosine; DNA demethylation; Amyloid peptide
Funding
- National Natural Science Foundation of China [31371309, 31400916]
- National Key Basic Research Program of China [2014CB943001]
- National Institutes of Health [NS079625, P50AG025688]
Ask authors/readers for more resources
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 beta 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 (A beta 1-42) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available