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DOI | 10.1038/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 |
ISSN | 2041-1723 |
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 |
URL | 查看原文 |
引用统计 | |
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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