title: Genome-wide alteration of 5-hydroxymenthylcytosine in a mouse model of Alzheimer's disease.
abstract: 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.
  
  
  
  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.
  
  
  
  5hmC-mediated epigenetic regulation could potentially be involved in the pathogenesis of AD.
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30022, USA.
authors.forename: Liqi
authors.initials: L
authors.lastname: Shu
authors.affiliation: Institute of Genetics, College of Life Sciences, Zhejiang University, 310058, Hangzhou, China.
authors.forename: Wenjia
authors.initials: W
authors.lastname: Sun
authors.affiliation: The Children's Hospital, School of Medicine, Zhejiang University, 310052, Hangzhou, China.|Institute of Translational Medicine, School of Medicine, Zhejiang University, 310029, Hangzhou, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30022, USA.|Department of Endocrinology, Wuhan Central Hospital, 430014, Wuhan, China.
authors.forename: Zihui
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30022, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: The Children's Hospital, School of Medicine, Zhejiang University, 310052, Hangzhou, China.|Institute of Translational Medicine, School of Medicine, Zhejiang University, 310029, Hangzhou, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Xie
authors.affiliation: The Children's Hospital, School of Medicine, Zhejiang University, 310052, Hangzhou, China.|Institute of Translational Medicine, School of Medicine, Zhejiang University, 310029, Hangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30022, USA.
authors.forename: Luoxiu
authors.initials: L
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, 30022, USA. peng.jin@emory.edu.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: The Children's Hospital, School of Medicine, Zhejiang University, 310052, Hangzhou, China. xuekun_li@zju.edu.cn.|Institute of Translational Medicine, School of Medicine, Zhejiang University, 310029, Hangzhou, China. xuekun_li@zju.edu.cn.
authors.forename: Xuekun
authors.initials: X
authors.lastname: Li
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000375:Aging / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D019175:DNA Methylation; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D055106:Genome-Wide Association Study; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine
keywords: 5-hydroxymethylcytosine; Alzheimer’s disease; Amyloid peptide; DNA demethylation