During brain development, neural progenitor cells (NPCs) give rise to various types of neurons and finally differentiate into astrocytes via switches in their differentiation competency. These switches involve changes in gene expression profiles that are thought to be governed partly by epigenetic control mechanisms, such as histone modification. Ryoichiro Kageyama and co-workers now report that the histone H3 Lys9 (H3K9) methyltransferase ESET (also known as Setdb1 or KMT1E) plays an essential role during mouse brain development (see p. 3806). ESET, they report, is highly expressed by mouse NPCs at early stages of brain development but is downregulated over time. Conditional ablation of ESET leads to reduced H3K9 trimethylation, misregulation of gene expression (including downregulation of neural gene expression, activation of non-neural gene expression and derepression of endogenous retroposons), severe brain defects and early lethality. Notably, loss of ESET impairs early neurogenesis but enhances astrocyte formation. Thus, the researchers suggest, ESET helps to regulate mouse brain development by epigenetically controlling temporal and tissue-specific gene expression.

© 2012. Published by The Company of Biologists Ltd
2012