Atoh1 is a key regulator of the differentiation of hair cells, the sensory cells that support audition: it is upregulated during their differentiation and downregulated at postnatal stages. But what are the mechanisms underlying Atoh1 transcriptional regulation during inner ear development? To address this question, Neil Segil and co-workers (p. ) analysed the epigenetic status of Atoh1 in mouse hair cell progenitors. They report that histone H3 at the Atoh1 locus is bivalently marked by the repressive tri-methylation of lysine 27 (H3K27me3) and the permissive tri-methylation of lysine K4 (H3K4me3). In nascent hair cells, Atoh1 upregulation is accompanied by a reduction in H3K27me3 and requires the appearance of the permissive acetylation of histone H3 lysine 9. At postnatal stages, Atoh1 downregulation is achieved by an increase in H3K9me3, which is a mark indicative of transcriptional silencing, and a reduction in histone H3 acetylation. In early postnatal supporting cells (a cell population that separates and surrounds hair cells and can regenerate them during the first postnatal week in mice), the bivalent marks are maintained, potentially explaining their latent regenerative capacity. This study suggests a mechanism for the epigenetic control of Atoh1 levels during inner ear development and reveals a potential target for future regenerative efforts to replace mammalian hair cells.
