Elevated H3K79 Homocysteinylation Causes Abnormal Gene Expression During Neural Development and Subsequent Neural Tube Defects

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Aug 26

PMID 30143612

Citations 43

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

Affiliations

Soon will be listed here.

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.

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