Long, S., Qiu, Y., Lin, T., Huang, S., Zhang, W., Liu, S., Tian, L., Palli, S.R., Li, S., Li, K. (2025). 20E-induced Kr-h1 expression facilitates developmental transitions depending on chromosome accessibility of BR-C enhancers.  Proc. Natl. Acad. Sci. U.S.A. 122(32): e2509608122.

FBrf0263106

Research paper

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 BR-C to sustain larval status in holometabolous insects. Here, we revealed that during the larval-prepupal transition in Drosophila melanogaster, the 20E-activated Kr-h1-BR-C axis is a prerequisite for wing disc morphogenesis. Mechanistically, 20E-EcR/USP-Met-Tai directly activates Kr-h1 that upregulates BR-C expression via the positive Kr-h1 binding sites (PKBS) in the BR-C enhancers. Furthermore, we showed that 20E-induced H3K27 acetylation increases chromatin accessibility of the PKBS-containing enhancers, facilitating the maximum of BR-C 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.

PMC12358878 (PMC) (EuropePMC)