title: An ecdysone-responsive nuclear receptor regulates circadian rhythms in Drosophila.
abstract: Little is known about molecular links between circadian clocks and steroid hormone signalling, although both are important for normal physiology. Here we report a circadian function for a nuclear receptor, ecdysone-induced protein 75 (Eip75/E75), which we identified through a gain-of-function screen for circadian genes in Drosophila melanogaster. Overexpression or knockdown of E75 in clock neurons disrupts rest:activity rhythms and dampens molecular oscillations. E75 represses expression of the gene encoding the transcriptional activator, CLOCK (CLK), and may also affect circadian output. PER inhibits the activity of E75 on the Clk promoter, thereby providing a mechanism for a previously proposed de-repressor effect of PER on Clk transcription. The ecdysone receptor is also expressed in central clock cells and manipulations of its expression produce effects similar to those of E75 on circadian rhythms. We find that E75 protects rhythms under stressful conditions, suggesting a function for steroid signalling in the maintenance of circadian rhythms in Drosophila.
authors.affiliation: Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Shailesh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Dechun
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Jang
authors.affiliation: Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nall
authors.affiliation: Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Xiangzhong
authors.initials: X
authors.lastname: Zheng
authors.affiliation: 1] Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA [2] Howard Hughes Medical Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Amita
authors.initials: A
authors.lastname: Sehgal
mesh_terms: D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics* / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: C120526:Clk protein, Drosophila; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C539040:PER protein, Drosophila; D056950:Period Circadian Proteins; D034741:RNA, Small Interfering; D011987:Receptors, Steroid; D014157:Transcription Factors; C055469:ecdysone receptor; C061375:Eip75B protein, Drosophila; D056926:CLOCK Proteins