20E-induced expression facilitates developmental transitions depending on chromosome accessibility of enhancers.

Transcription factors and histone modification-mediated chromatin accessibility coordinately regulate spatiotemporal expression of genes that control growth and development. It is well documented that juvenile hormone-activated Kr-h1 antagonizes 20-hydroxyecdysone (20E)-induced expression of the pupal specifier to sustain larval status in holometabolous insects. Here, we revealed that during the larval-prepupal transition in , the 20E-activated axis is a prerequisite for wing disc morphogenesis. Mechanistically, 20E-EcR/USP-Met-Tai directly activates Kr-h1 that upregulates expression via the positive Kr-h1 binding sites (PKBS) in the enhancers. Furthermore, we showed that 20E-induced H3K27 acetylation increases chromatin accessibility of the PKBS-containing enhancers, facilitating the maximum of expression that promotes developmental transitions. Collectively, in response to different hormone stimuli, a single transcription factor either negatively or positively regulates the expression of the same target gene depending on chromatin accessibility of its different enhancer regions, thus manipulating distinct developmental events.