title: Diverse Hormone Response Networks in 41 Independent Drosophila Cell Lines.
abstract: Steroid hormones induce cascades of gene activation and repression with transformative effects on cell fate . Steroid transduction plays a major role in the development and physiology of nearly all metazoan species, and in the progression of the most common forms of cancer. Despite the paramount importance of steroids in developmental and translational biology, a complete map of transcriptional response has not been developed for any hormone . In the case of 20-hydroxyecdysone (ecdysone) in Drosophila melanogaster, these trajectories range from apoptosis to immortalization. We mapped the ecdysone transduction network in a cohort of 41 cell lines, the largest such atlas yet assembled. We found that the early transcriptional response mirrors the distinctiveness of physiological origins: genes respond in restricted patterns, conditional on the expression levels of dozens of transcription factors. Only a small cohort of genes is constitutively modulated independent of initial cell state. Ecdysone-responsive genes tend to organize into directional same-stranded units, with consecutive genes induced from the same strand. Here, we identify half of the ecdysone receptor heterodimer as the primary rate-limiting step in the response, and find that initial receptor isoform levels modulate the activated cohort of target transcription factors. This atlas of steroid response reveals organizing principles of gene regulation by a model type II nuclear receptor and lays the foundation for comprehensive and predictive understanding of the ecdysone transduction network in the fruit fly.
authors.affiliation: Department of Biostatistics, University of California Berkeley, California 94720 Department of Genome Dynamics, Lawrence Berkeley National Laboratory, California 94720.
authors.forename: Marcus
authors.initials: M
authors.lastname: Stoiber
authors.affiliation: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, California 94720.
authors.forename: Susan
authors.initials: S
authors.lastname: Celniker
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana 47405.
authors.forename: Lucy
authors.initials: L
authors.lastname: Cherbas
authors.affiliation: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, California 94720 Department of Statistics, University of California Berkeley, California 94720 JBBrown@lbl.gov cherbas@indiana.edu.
authors.forename: Ben
authors.initials: B
authors.lastname: Brown
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana 47405 JBBrown@lbl.gov cherbas@indiana.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Cherbas
mesh_terms: D000818:Animals; D002460:Cell Line; D016000:Cluster Analysis; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D004440:Ecdysone / Q000378:metabolism / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006728:Hormones / Q000378:metabolism* / Q000494:pharmacology; D020033:Protein Isoforms; D011987:Receptors, Steroid / Q000378:metabolism; D015398:Signal Transduction; D013256:Steroids / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D059467:Transcriptome
chemical_list: D006728:Hormones; D020033:Protein Isoforms; D011987:Receptors, Steroid; D013256:Steroids; D014157:Transcription Factors; C055469:ecdysone receptor; D004440:Ecdysone
keywords: RNA-seq; bioinformatics; ecdysone; network biology; transcription