4.7 Article

Loss of Wiz Function Affects Methylation Pattern in Palate Development and Leads to Cleft Palate

期刊

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.620692

关键词

Wiz; G9a; GLP; histone methylation; cleft palate; development; craniofacial

资金

  1. National Sustainability Program II by the Ministry of Education, the Youth and Sports of the Czech Republic (MEYS) [LQ1604]
  2. Czech Centre for Phenogenomics by the Ministry of Education, the Youth and Sports of the Czech Republic (MEYS) [LM2015040, LM2018126]
  3. Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University in Vestec (BIOCEV) [CZ.1.05/1.1.00/02.0109]
  4. Higher quality and capacity for transgenic models by MEYS [CZ.1.05/2.1.00/19.0395]
  5. European Regional Development fund by MEYS
  6. Upgrade of the Czech Centre for Phenogenomics: developing toward translation research by MEYS [CZ.02.1.01/0.0/0.0/16_013/0001789]
  7. European Structural Investment Fund by Czech Science Foundation
  8. project Deciphering biological role of ZNF644 to edit the activity of G9a/GLP methylation complex (GACR) by Czech Science Foundation [19-21696S]

向作者/读者索取更多资源

The study found that in the WIZ knockout mouse model, defective embryos exhibited abnormalities in multiple aspects during development, particularly in the craniofacial region, such as shorter snout, cleft palate, and cleft eyelids. These results suggest that WIZ plays an important role in craniofacial development.
WIZ (Widely Interspaced Zinc Finger) is associated with the G9a-GLP protein complex, a key H3K9 methyltransferase suggesting a role in transcriptional repression. However, its role in embryonic development is poorly described. In order to assess the loss of function of WIZ, we generated CRISPR/Cas9 WIZ knockout mouse model with 32 nucleotide deletion. Observing the lethality status, we identified the WIZ knockouts to be subviable during embryonic development and non-viable after birth. Morphology of developing embryo was analyzed at E14.5 and E18.5 and our findings were supported by microCT scans. Wiz KO showed improper development in multiple aspects, specifically in the craniofacial area. In particular, shorter snout, cleft palate, and cleft eyelids were present in mutant embryos. Palatal shelves were hypomorphic and though elevated to a horizontal position on top of the tongue, they failed to make contact and fuse. By comparison of proliferation pattern and histone methylation in developing palatal shelves we brought new evidence of importance WIZ dependent G9a-GLP methylation complex in craniofacial development, especially in palate shelf fusion.

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