GRHL3 基因低甲基化与神经管缺陷的发生有关。
Hypomethylation of GRHL3 gene is associated with the occurrence of neural tube defects.
机构信息
Institute of Reproductive & Child Health, Ministry of Health Key Laboratory of Reproductive Health, Department of Epidemiology & Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, PR China.
Key Laboratory of Cell Proliferation & Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing, PR China.
出版信息
Epigenomics. 2018 Jul;10(7):891-901. doi: 10.2217/epi-2018-0016. Epub 2018 Mar 28.
AIM
To investigate the relationship between GRHL3 methylation and the etiology of neural tube defects (NTDs).
MATERIALS & METHODS: Analyze data from a genome-wide DNA methylation array. Targeted DNA methylation analysis was performed for 46 cases and 23 controls. At last, grhl3 overexpression and gene depletion experiments were conducted in zebrafish.
RESULTS
Five hypomethylated CpGs were discovered in the methylation arrays performed on NTD cases. In a validation study, 15 hypomethylated CpGs were found and the overall methylation levels decreased in brain/spinal cord tissue from NTD cases. The knockdown and overexpression of grhl3 in zebrafish damaged embryonic convergent extension processes.
CONCLUSION
Hypomethylation of GRHL3 in central nervous tissue is associated with NTDs, further supporting the importance of GRHL3 and methylation in proper neural tube closure.
目的
探讨 GRHL3 甲基化与神经管缺陷（NTDs）病因之间的关系。
材料与方法
分析全基因组 DNA 甲基化阵列的数据。对 46 例病例和 23 例对照进行了靶向 DNA 甲基化分析。最后，在斑马鱼中进行了 grhl3 过表达和基因缺失实验。
结果
在对 NTD 病例进行的甲基化阵列中发现了 5 个低甲基化 CpG。在验证研究中，发现了 15 个低甲基化 CpG，并且 NTD 病例的脑/脊髓组织中的整体甲基化水平降低。在斑马鱼中敲低和过表达 grhl3 会破坏胚胎的会聚延伸过程。
结论
中枢神经系统中 GRHL3 的低甲基化与 NTDs 相关，进一步支持了 GRHL3 和甲基化在适当的神经管闭合中的重要性。
Zotero 插件