title: 20-Hydroxyecdysone (20E) Primary Response Gene E75 Isoforms Mediate Steroidogenesis Autoregulation and Regulate Developmental Timing in Bombyx.
abstract: 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.
authors.affiliation: 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.
authors.forename: Kang
authors.initials: K
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Ling
authors.initials: L
authors.lastname: Tian
authors.affiliation: the Institute of Life Sciences, Jiangsu University, Zhengjiang 212013, Jiangsu, China.
authors.forename: Zhongjian
authors.initials: Z
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Sanyou
authors.initials: S
authors.lastname: Guo
authors.affiliation: the Research Institute of Applied Biology and College of Life Science, Shanxi University, Taiyuan, Shanxi, 030006, China.
authors.forename: Jianzhen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: the Department of Biology, National Museum of Natural Science, 1 Kuan-Chien Road, Taichung 404, Taiwan, and.
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Gu
authors.affiliation: the Department of Entomology, College of Agriculture, University of Kentucky, Lexington, Kentucky 40546.
authors.forename: Subba R
authors.initials: SR
authors.lastname: Palli
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cao
authors.affiliation: 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, lisheng@scnu.edu.cn lisheng01@sibs.ac.cn.
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D012831:Bombyx / Q000196:embryology* / Q000235:genetics; D004441:Ecdysterone / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D017344:Genes, Insect / Q000502:physiology*; D019476:Insect Proteins / Q000096:biosynthesis* / Q000235:genetics; D008675:Metamorphosis, Biological / Q000502:physiology*; D020033:Protein Isoforms
chemical_list: D019476:Insect Proteins; D020033:Protein Isoforms; D004441:Ecdysterone
keywords: Halloween genes; ROREs; development; feedback regulation; isoform-specific; nuclear receptor; protein-protein interaction; signal transduction; steroidogenesis