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ASH2L, Core Subunit of H3K4 Methylation Complex, Regulates Amelogenesis
X Zhu1,2,3,4,5, Z Ma1,2,3,4,5, F Xie1,2,3,4,5
1Department of Pediatric Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Journal of Dental Research
|November 22, 2023
Summary
ASH2L regulates enamel formation by controlling H3K4me3 methylation. Its absence disrupts dental germ development, leading to abnormal cell behavior and impaired tooth formation.
Area of Science:
- Developmental Biology
- Epigenetics
- Oral Biology
Background:
- Histone methylation, specifically H3K4me3, is vital for enamel development.
- ASH2L is a key component in establishing H3K4me3 marks.
Purpose of the Study:
- To investigate the role of ASH2L-mediated H3K4me3 modification in amelogenesis.
- To elucidate the molecular mechanisms underlying ASH2L's function in tooth development.
Main Methods:
- Conditional knockout of Ash2l in mouse dental epithelium.
- Cut&Tag-seq (cleavage under targets and tagmentation sequencing) analysis.
- Real-time PCR, immunohistochemistry, and immunofluorescence.
Main Results:
- Ash2l knockout reduced H3K4me3, causing abnormal dental germ morphology and loss of cell polarity.
- Dysregulated proliferation and apoptosis of inner enamel epithelium cells were observed.
- Downregulation of key genes (Amelx, Dspp, Shh, Sp6, Trp63 isomers) and impaired enamel/dentin formation occurred.
Conclusions:
- ASH2L, via H3K4me3, regulates critical amelogenesis genes (Shh, Trp63).
- Loss of ASH2L and H3K4me3 leads to aberrant dental epithelial cell behavior and amelogenesis defects.
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