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

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.

Keywords: GRHL3 gene; PCP pathway; methylation; neural tube defects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Case-Control Studies
  • CpG Islands
  • DNA Methylation
  • DNA-Binding Proteins / genetics*
  • Fetus
  • Humans
  • Neural Tube Defects / genetics*
  • Transcription Factors / genetics*
  • Zebrafish Proteins / genetics


  • DNA-Binding Proteins
  • GRHL3 protein, human
  • GRHL3 protein, zebrafish
  • Transcription Factors
  • Zebrafish Proteins