20E-induced Kr-h1 expression facilitates developmental transitions depending on chromosome accessibility of BR-C enhancers

• 成果类型: Article
• 署名作者: Long, Shihui; Qiu, Yongyu; Lin, Tong; Huang, Shumin; Zhang, Wenhao; Liu, Suning; Tian, Ling; Palli, Subba R.; Li, Sheng; Li, Kang
• 署名单位: South China Normal University; Huaihua University; Guangdong Laboratory for Lingnan Modern Agriculture; University of Kentucky; South China Normal University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13780
• DOI: 10.1073/pnas.2509608122
• 发表日期: 2025-08-12
• 关键词: kruppel homolog 1; juvenile-hormone action; methoprene-tolerant; broad-complex; ecdysone response; prothoracic gland; drosophila; receptor; protein; met

摘要

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.