Epigenomics · 2019
Low folate concentration impacts mismatch repair deficiency in neural tube defects.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Li Huili, Wang Xiaolei, Zhao Huizhi, Wang Fang, Bao Yihua, Guo Jin, Chang Shaoyan, Wu Lihua, Cheng Haiqin, Chen Shuyuan, Zou Jizhen, Cui Xiaodai, Niswander Lee, Finnell Richard H, Wang Hongyan, Zhang Ting
Аннотация
Aim: To know the cause of sequence variants in neural tube defect (NTD). Materials & methods: We sequenced genes implicated in neural tube closure (NTC) in a Chinese cohort and elucidated the molecular mechanism-driving mutations. Results: In NTD cases, an increase in specific variants was identified, potentially deleterious rare variants harbored in H3K36me3 occupancy regions that recruits mismatch repair (MMR) machinery. Lower folate concentrations in local brain tissues were also observed. In neuroectoderm cells, folic acid insufficiency attenuated association of Msh6 to H3K36me3, and reduced bindings to NTC genes. Rare variants in human NTDs were featured by MMR deficiency and more severe microsatellite instability. Conclusion: Our work suggests a mechanistic link between folate insufficiency and MMR deficiency that correlates with an increase of rare variants in NTC genes.