Hypomethylation of GRHL3 Gene is Associated with the Occurrence of Neural Tube Defects

Abstract

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.

Keywords::

• GRHL3 gene
• methylation
• neural tube defects
• PCP pathway

Supplementary data

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Financial & competing interests disclosure

This work was supported by grants from the National Natural Science Foundation of China (Grants No. 81472987 and 81773441, 81371264); Beijing Natural Science Foundation (Grant No. 7162094); and the National Key Research and Development Program, Ministry of Science and Technology, PR China (Grant No. 2016YFC1000501). Peking University Health Science Center Interdisciplinary Research Seed Fund (No. BMU20140446). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study was approved by the institutional review board of Peking University and the mothers provided written informed consent.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China (Grants No. 81472987 and 81773441, 81371264); Beijing Natural Science Foundation (Grant No. 7162094); and the National Key Research and Development Program, Ministry of Science and Technology, PR China (Grant No. 2016YFC1000501). Peking University Health Science Center Interdisciplinary Research Seed Fund (No. BMU20140446). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.