Genome-wide alteration of 5-hydroxymenthylcytosine in a mouse model of Alzheimer’s disease

BMC Genomics

Research Article

Liqi Shu¹  Li Lin¹  Luoxiu Huang¹  Peng Jin¹  Zihui Xu²  Wenjia Sun³  Qi Xu⁴  Liping Li⁵  Xuekun Li⁵  Pei Xie⁵  Hui Shen⁵ 

[1] Department of Human Genetics, Emory University School of Medicine, 30022, Atlanta, GA, USA;Department of Human Genetics, Emory University School of Medicine, 30022, Atlanta, GA, USA;Department of Endocrinology, Wuhan Central Hospital, 430014, Wuhan, China;Institute of Genetics, College of Life Sciences, Zhejiang University, 310058, Hangzhou, China;National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, 100005, Beijing, China;The Children’s Hospital, School of Medicine, Zhejiang University, 310052, Hangzhou, China;Institute of Translational Medicine, School of Medicine, Zhejiang University, 310029, Hangzhou, China;

关键词: Alzheimer’s disease;    5-hydroxymethylcytosine;    DNA demethylation;    Amyloid peptide;   

DOI  :  10.1186/s12864-016-2731-1

 received in 2015-10-22, accepted in 2016-05-12,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundAlzheimer’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.ResultsWe 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.Conclusions5hmC-mediated epigenetic regulation could potentially be involved in the pathogenesis of AD.

【 授权许可】

CC BY   
© Shu et al. 2016