GSTDTAP  > 资源环境科学
DOI10.1038/s41467-018-06429-1
Elevated H3K79 homocysteinylation causes abnormal gene expression during neural development and subsequent neural tube defects
Zhang, Qin1; Bai, Baoling1; Mei, Xinyu2,3; Wan, Chunlei1; Cao, Haiyan1; Li, Dan1,4; Wang, Shan1; Zhang, Min1; Wang, Zhigang5,6; Wu, Jianxin1; Wang, Hongyan2,3; Huo, Junsheng7; Ding, Gangqiang7; Zhao, Jianyuan8,9; Xie, Qiu5,6; Wang, Li1; Qiu, Zhiyong1; Zhao, Shiming2,3; Zhang, Ting1
2018-08-24
发表期刊NATURE COMMUNICATIONS
ISSN2041-1723
出版年2018
卷号9
文章类型Article
语种英语
国家Peoples R China
英文摘要

Neural tube defects (NTDs) are serious congenital malformations. Excessive maternal homocysteine (Hcy) increases the risk of NTDs, while its mechanism remains elusive. Here we report the role of histone homocysteinylation in neural tube closure (NTC). A total of 39 histone homocysteinylation sites are identified in samples from human embryonic brain tissue using mass spectrometry. Elevated levels of histone KHcy and H3K79Hcy are detected at increased cellular Hcy levels in human fetal brains. Using ChIP-seq and RNA-seq assays, we demonstrate that an increase in H3K79Hcy level down-regulates the expression of selected NTC-related genes including Cecr2, Smarca4, and Dnmt3b. In human NTDs brain tissues, decrease in expression of CECR2, SMARCA4, and DNMT3B is also detected along with high levels of Hcy and H3K79Hcy. Our results suggest that higher levels of Hcy contribute to the onset of NTDs through up-regulation of histone H3K79Hcy, leading to abnormal expressions of selected NTC-related genes.


领域资源环境
收录类别SCI-E
WOS记录号WOS:000442594800038
WOS关键词ONE-CARBON METABOLISM ; CHROMATIN REMODELING COMPLEX ; HISTONE MODIFICATIONS ; HUMAN GENOME ; PATHOLOGICAL CONSEQUENCES ; POSSIBLE MECHANISM ; MASS-SPECTROMETRY ; MOUSE EMBRYOS ; IN-VITRO ; EPIGENETICS
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
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引用统计
被引频次:49[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/204006
专题资源环境科学
作者单位1.Capital Inst Pediat, Beijing Municipal Key Lab Child Dev & Nutri, Beijing 100020, Peoples R China;
2.Fudan Univ, Obstet & Gynecol Hosp, State Key Lab Genet Engn, Shanghai 200433, Peoples R China;
3.Inst Biomed Sci, Shanghai 200433, Peoples R China;
4.Weifang Med Univ, Weifang 261053, Peoples R China;
5.Chinese Acad Med Sci, Beijing 100005, Peoples R China;
6.Peking Union Med Coll, Beijing 100005, Peoples R China;
7.Chinese Ctr Dis Control & Prevent, Key Lab Trace Element Nutr, Natl Hlth & Family Planning Commiss Peoples Repub, Natl Inst Nutr & Hlth, Beijing 102206, Peoples R China;
8.Fudan Univ, State Key Lab Genet Engn, Shanghai 200438, Peoples R China;
9.Fudan Univ, Sch Life Sci, Shanghai 200438, Peoples R China
推荐引用方式
GB/T 7714
Zhang, Qin,Bai, Baoling,Mei, Xinyu,et al. Elevated H3K79 homocysteinylation causes abnormal gene expression during neural development and subsequent neural tube defects[J]. NATURE COMMUNICATIONS,2018,9.
APA Zhang, Qin.,Bai, Baoling.,Mei, Xinyu.,Wan, Chunlei.,Cao, Haiyan.,...&Zhang, Ting.(2018).Elevated H3K79 homocysteinylation causes abnormal gene expression during neural development and subsequent neural tube defects.NATURE COMMUNICATIONS,9.
MLA Zhang, Qin,et al."Elevated H3K79 homocysteinylation causes abnormal gene expression during neural development and subsequent neural tube defects".NATURE COMMUNICATIONS 9(2018).
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