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.

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Published in Journal of Biological Chemistry, v. 291, no. 35, p. 18163-18175.

This research was originally published in the Journal of Biological Chemistry. Li, K., Tian, L., Guo, Z., Guo, S., Zhang, J., Gu, S., Palli, S., Cao, Y., and Li, S. 20-Hydroxyecdysone (20E) Primary Response Gene E75 Isoforms Mediate Steroidogenesis Autoregulation and Regulate Developmental Timing in Bombyx. J. Biol. Chem. 2016; 291: 18163-18175. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences Grant XDB13030700 (to S. L.), 973 Program 2012CB114600 (to S. L. and Y. C.), National Science Foundation of China Grants 31572325 (to S. L.) and 31472042 (to L. T.), and National Program for the Development of New Transgenic Species of China Grant 2014ZX08010-016B (to S. L.).

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This article contains supplemental Figs. S1–S5.

jbc.M116.737072-1.pdf (1455 kB)
Supplementary Figures and Figure Legends: Figure S1-S5.