Enhancer activation by FGF signalling during otic induction

Abstract Vertebrate ear progenitors are induced by fibroblast growth factor signalling, however the molecular mechanisms leading to the coordinate activation of downstream targets are yet to be discovered. The ear, like other sensory placodes, arises from the pre-placodal region at the border of the neural plate. Using a multiplex NanoString approach, we determined the response of these progenitors to FGF signalling by examining the changes of more than 200 transcripts that define the otic and other placodes, neural crestand neural plateterritories. This analysis identifies new direct and indirect FGF targets during otic induction. Investigating changes in histone marks by ChIP-seq reveals that FGF exposure of pre-placodal cells leads to rapid deposition of active chromatin marks H3K27ac near FGF-response genes, while H3K27ac is depleted in the vicinity of non-otic genes. Genomic regions that gain H3K27ac act as cis-regulatory elementscontrolling otic gene expression in time and space and define a unique transcription factor signature likely to control their activity. Finally, we show that in response to FGF signalling the transcription factor dimer AP1 recruits the histone acetyl transferase p300 to selected otic enhancers. Thus, during ear induction FGF signalling modifies the chromatin landscape to promote enhancer activation and chromatin accessibility.