Elevated H3K79 homocysteinylation causes abnormal gene expression during neural development and subsequent neural tube defects View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Qin Zhang, Baoling Bai, Xinyu Mei, Chunlei Wan, Haiyan Cao, Dan Li, Shan Wang, Min Zhang, Zhigang Wang, Jianxin Wu, Hongyan Wang, Junsheng Huo, Gangqiang Ding, Jianyuan Zhao, Qiu Xie, Li Wang, Zhiyong Qiu, Shiming Zhao, Ting Zhang

ABSTRACT

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. More... »

PAGES

3436

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-05451-7

    DOI

    http://dx.doi.org/10.1038/s41467-018-05451-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1106257045

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30143612


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