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Epigenomics. 2018 Jul;10(7):891-901. doi: 10.2217/epi-2018-0016. Epub 2018 Mar 28.

Hypomethylation of GRHL3 gene is associated with the occurrence of neural tube defects.

Author information

1
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.
2
Key Laboratory of Cell Proliferation & Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing, PR China.
3
Departments of Molecular & Cellular Biology & Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

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; PCP pathway; methylation; neural tube defects

PMID:
29587534
PMCID:
PMC6077761
DOI:
10.2217/epi-2018-0016
[Indexed for MEDLINE]
Free PMC Article

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