FGF signalling regulates enhancer activation during ear progenitor induction

The fibroblast growth factor pathway is essential for inner earinduction in many vertebrates, however how it regulates the chromatinlandscape to coordinate the activation of otic genes remains unclear. Here we show that FGF exposure of sensory progenitors leads to rapid deposition of active chromatinmarks H3K27ac near hundreds of FGF-responsive, otic-epibranchial progenitor (OEP) genes, while H3K27ac is depleted in the vicinity of non-otic genes. Genomic regions that gain H3K27ac act as cis-regulatory elementscontrolling OEP gene expression in time and space and define a unique transcription factor signature likely to control their activity. Finally, we provide evidence that in response to FGF signalling the transcription factor dimer AP1 recruits the histone acetyl transferase p300 to OEP enhancers and that de novo acetylation is required for subsequent expression of OEP genes. Thus, during ear induction FGF signalling modifies the chromatinlandscape to promote enhancer activation and chromatinaccessibility.