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20E诱导的表达根据增强子的染色体可及性促进发育转变。

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

作者信息

Long Shihui, Qiu Yongyu, Lin Tong, Huang Shumin, Zhang Wenhao, Liu Suning, Tian Ling, Palli Subba R, Li Sheng, Li Kang

机构信息

Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology, Institute of Insect Science and Technology, School of Life Sciences, South China Normal University, Guangzhou 510631, China.

College of Biological and Food Engineering, Huaihua University, Huaihua 418000, China.

出版信息

Proc Natl Acad Sci U S A. 2025 Aug 12;122(32):e2509608122. doi: 10.1073/pnas.2509608122. Epub 2025 Aug 7.

DOI:10.1073/pnas.2509608122
PMID:40773235
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12358878/
Abstract

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.

摘要

转录因子和组蛋白修饰介导的染色质可及性协同调节控制生长和发育的基因的时空表达。有充分的文献记载,保幼激素激活的Kr-h1拮抗20-羟基蜕皮激素(20E)诱导的蛹期决定因子的表达,以维持全变态昆虫的幼虫状态。在这里,我们揭示了在 幼虫-预蛹转变期间,20E激活的 轴是翅芽形态发生的先决条件。从机制上讲,20E-EcR/USP-Met-Tai直接激活Kr-h1,Kr-h1通过 增强子中的正向Kr-h1结合位点(PKBS)上调 表达。此外,我们表明20E诱导的H3K27乙酰化增加了含PKBS的增强子的染色质可及性,促进了促进发育转变的 表达的最大化。总的来说,响应不同的激素刺激,单个转录因子根据其不同增强子区域的染色质可及性对同一靶基因的表达进行负向或正向调节,从而操纵不同的发育事件。