Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Development. 2012 Oct;139(20):3806-16. doi: 10.1242/dev.082198.
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.
在发育中的大脑中，神经祖细胞通过改变受表观遗传控制（如组蛋白修饰）的基因表达谱来切换分化能力，尽管确切的机制尚不清楚。在这里，我们发现 ESET（Setdb1），一种组蛋白 H3 赖氨酸 9（H3K9）甲基转移酶，在小鼠大脑发育的早期高度表达，但随着时间的推移下调，并且 ESET 的缺失导致 H3K9 三甲基化减少和基因调控失常，导致严重的大脑缺陷和早期致死。在突变体大脑中，内源性逆转录转座子被解除抑制，非神经基因表达被激活。此外，早期神经发生严重受损，而星形胶质细胞形成增强。我们得出结论，ESET 在时间和组织特异性基因表达中具有表观遗传作用，从而对大脑发育进行适当的控制。
