Journal
DEVELOPMENT
Volume 139, Issue 20, Pages 3806-3816Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.082198
Keywords
ESET; Astrocyte; Epigenetic control; Histone methyltransferase; Neural progenitor
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- MEXT scholarship of the Ministry of Education, Culture, Sports, Science and Technology of Japan
- Grants-in-Aid for Scientific Research [22123002] Funding Source: KAKEN
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In the developing brain, neural progenitor cells switch differentiation competency by changing gene expression profiles that are governed partly by epigenetic control, such as histone modification, although the precise mechanism is unknown. Here we found that ESET (Setdb1), a histone H3 Lys9 (H3K9) methyltransferase, is highly expressed at early stages of mouse brain development but downregulated over time, and that ablation of ESET leads to decreased H3K9 trimethylation and the misregulation of genes, resulting in severe brain defects and early lethality. In the mutant brain, endogenous retrotransposons were derepressed and non-neural gene expression was activated. Furthermore, early neurogenesis was severely impaired, whereas astrocyte formation was enhanced. We conclude that there is an epigenetic role of ESET in the temporal and tissue-specific gene expression that results in proper control of brain development.
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