Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntingtons disease
Wang, Fengli1; Yang, Yeran2; Lin, Xiwen3; Wang, Jiu-Qiang1; Wu, Yong-Sheng2; Xie, Wenjuan1; Wang, Dandan1; Zhu, Shu1; Liao, You-Qi2; Sun, Qinmiao1; Yang, Yun-Gui2; Luo, Huai-Rong4; Guo, Caixia2; Han, Chunsheng3; Tang, Tie-Shan1
2013-09-15
发表期刊HUMAN MOLECULAR GENETICS
ISSN0964-6906
卷号22期号:18页码:3641-3653
摘要5-Hydroxymethylcytosine (5-hmC) may represent a new epigenetic modification of cytosine. While the dynamics of 5-hmC during neurodevelopment have recently been reported, little is known about its genomic distribution and function(s) in neurodegenerative diseases such as Huntingtons disease (HD). We here observed a marked reduction of the 5-hmC signal in YAC128 (yeast artificial chromosome transgene with 128 CAG repeats) HD mouse brain tissues when compared with age-matched wild-type (WT) mice, suggesting a deficiency of 5-hmC reconstruction in HD brains during postnatal development. Genome-wide distribution analysis of 5-hmC further confirmed the diminishment of the 5-hmC signal in striatum and cortex in YAC128 HD mice. General genomic features of 5-hmC are highly conserved, not being affected by either disease or brain regions. Intriguingly, we have identied disease-specific (YAC128 versus WT) differentially hydroxymethylated regions (DhMRs), and found that acquisition of DhmRs in gene body is a positive epigenetic regulator for gene expression. Ingenuity pathway analysis (IPA) of genotype-specific DhMR-annotated genes revealed that alternation of a number of canonical pathways involving neuronal development/differentiation (Wnt/-catenin/Sox pathway, axonal guidance signaling pathway) and neuronal function/survival (glutamate receptor/calcium/CREB, GABA receptor signaling, dopamine-DARPP32 feedback pathway, etc.) could be important for the onset of HD. Our results indicate that loss of the 5-hmC marker is a novel epigenetic feature in HD, and that this aberrant epigenetic regulation may impair the neurogenesis, neuronal function and survival in HD brain. Our study also opens a new avenue for HD treatment; re-establishing the native 5-hmC landscape may have the potential to slow/halt the progression of HD.
关键词Embryonic Stem-cells Adult Hippocampal Neurogenesis Transgenic Mouse Model Dna Methylation Gene-expression Mutant Huntingtin Nervous-system Polyglutamine Pathogenesis Mitochondrial Dysfunction Mammalian Development
资助信息National Basic Research Program of China [2011CB965003, 2012CB944702]; NSFC [30970931, 30970588, 31170730]; Knowledge Innovation Program of Chinese Academy of Sciences [KSCX2-YW-R-148]; One-Hundred-Talent Program of CAS
学科领域Biochemistry & Molecular Biology ; Genetics & Heredity
收录类别SCI
语种英语
WOS研究方向Biochemistry & Molecular Biology ; Genetics & Heredity
WOS类目Biochemistry & Molecular Biology ; Genetics & Heredity
WOS记录号WOS:000323582000003
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被引频次:65[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/16661
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China
2.Chinese Acad Sci, Beijing Inst Genom, Lab Dis Genom & Individual Med, Beijing 100101, Peoples R China
3.Chinese Acad Sci, Inst Zool, State Key Lab Reprod Biol, Beijing 100101, Peoples R China
4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem, Kunming 650201, Yunnan, Peoples R China
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Wang, Fengli,Yang, Yeran,Lin, Xiwen,et al. Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntingtons disease[J]. HUMAN MOLECULAR GENETICS,2013,22(18):3641-3653.
APA Wang, Fengli.,Yang, Yeran.,Lin, Xiwen.,Wang, Jiu-Qiang.,Wu, Yong-Sheng.,...&Tang, Tie-Shan.(2013).Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntingtons disease.HUMAN MOLECULAR GENETICS,22(18),3641-3653.
MLA Wang, Fengli,et al."Genome-wide loss of 5-hmC is a novel epigenetic feature of Huntingtons disease".HUMAN MOLECULAR GENETICS 22.18(2013):3641-3653.
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