Li Kang, Tian Ling, Guo Zhongjian, Guo Sanyou, Zhang Jianzhen, Gu Shi-Hong, Palli Subba R, Cao Yang, Li Sheng
From the Guangzhou Key Laboratory of Insect Development Regulation and Application Research, Institute of Insect Sciences and School of Life Sciences, South China Normal University, Guangzhou 510631, China, the Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
the Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China, the Laboratory of Insect Molecular Biology and Biotechnology, Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding, College of Animal Sciences, South China Agricultural University, Guangzhou 510642, China.
J Biol Chem. 2016 Aug 26;291(35):18163-75. doi: 10.1074/jbc.M116.737072. Epub 2016 Jun 29.
The temporal control mechanisms that precisely control animal development remain largely elusive. The timing of major developmental transitions in insects, including molting and metamorphosis, is coordinated by the steroid hormone 20-hydroxyecdysone (20E). 20E involves feedback loops to maintain pulses of ecdysteroid biosynthesis leading to its upsurge, whereas the underpinning molecular mechanisms are not well understood. Using the silkworm Bombyx mori as a model, we demonstrated that E75, the 20E primary response gene, mediates a regulatory loop between ecdysteroid biosynthesis and 20E signaling. E75 isoforms A and C directly bind to retinoic acid receptor-related response elements in Halloween gene promoter regions to induce gene expression thus promoting ecdysteroid biosynthesis and developmental transition, whereas isoform B antagonizes the transcriptional activity of isoform A/C through physical interaction. As the expression of E75 isoforms is differentially induced by 20E, the E75-mediated regulatory loop represents a fine autoregulation of steroidogenesis, which contributes to the precise control of developmental timing.
精确控制动物发育的时间控制机制在很大程度上仍然难以捉摸。昆虫主要发育转变的时间，包括蜕皮和变态，是由类固醇激素20-羟基蜕皮激素（20E）协调的。20E涉及反馈回路以维持蜕皮甾体生物合成的脉冲，从而导致其激增，而其潜在的分子机制尚不清楚。以家蚕为模型，我们证明了20E初级反应基因E75介导了蜕皮甾体生物合成与20E信号传导之间的调节回路。E75同工型A和C直接结合到万圣节基因启动子区域中的视黄酸受体相关反应元件上以诱导基因表达，从而促进蜕皮甾体生物合成和发育转变，而异工型B通过物理相互作用拮抗同工型A/C的转录活性。由于E75同工型的表达受到20E的差异诱导，E75介导的调节回路代表了类固醇生成的精细自动调节，这有助于精确控制发育时间。
