Genome-Wide Expression Analysis in DrosophilaReveals Genes Controlling Circadian Behavior

In Drosophila, a number of key processes such as emergence from the pupal case, locomotor activity, feeding, olfaction, and aspects of mating behavior are under circadian regulation. Although we have a basic understanding of how the molecular oscillations take place, a clear link between gene regulation and downstream biological processes is still missing. To identify clock-controlled output genes, we have used an oligonucleotide-based high-density array that interrogates gene expression changes on a whole genome level. We found genes regulating various physiological processes to be under circadian transcriptional regulation, ranging from protein stability and degradation, signal transduction, heme metabolism, detoxification, and immunity. By comparing rhythmically expressed genes in the fly head and body, we found that the clock has adapted its output functions to the needs of each particular tissue, implying that tissue-specific regulation is superimposed on clock control of gene expression. Finally, taking full advantage of the fly as a model system, we have identified and characterized a cycling potassium channel protein as a key step in linking the transcriptional feedback loop to rhythmic locomotor behavior.

[1]  B. Ganetzky,et al.  A Drosophila mutation that eliminates a calcium-dependent potassium current. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[2]  G. Block,et al.  The Bulla ocular circadian pacemaker. I. Pacemaker neuron membrane potential controls phase through a calcium-dependent mechanism. , 1987, Journal of comparative physiology. A, Sensory, neural, and behavioral physiology.

[3]  C. Haass,et al.  The Drosophila proteasome undergoes changes in its subunit pattern during development. , 1989, Experimental cell research.

[4]  Miriam Khen,et al.  Odorant signal termination by olfactory UDP glucuronosyl transferase , 1991, Nature.

[5]  N. Atkinson,et al.  A component of calcium-activated potassium channels encoded by the Drosophila slo locus. , 1991, Science.

[6]  Jeffrey C. Hall,et al.  Behavior in Light-Dark Cycles of Drosophila Mutants That Are Arrhythmic, Blind, or Both , 1993, Journal of biological rhythms.

[7]  G. Block,et al.  Circadian rhythm in membrane conductance expressed in isolated neurons. , 1993, Science.

[8]  J. Belote,et al.  Identification of an essential gene, l(3)73Ai, with a dominant temperature-sensitive lethal allele, encoding a Drosophila proteasome subunit. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[9]  P. Hardin Analysis of period mRNA cycling in Drosophila head and body tissues indicates that body oscillators behave differently from head oscillators , 1994, Molecular and cellular biology.

[10]  R. Brenner,et al.  Tissue-specific expression of a Drosophila calcium-activated potassium channel , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  M. Krasnow,et al.  Extent and character of circadian gene expression in Drosophila melanogaster: identification of twenty oscillating mRNAs in the fly head , 1995, Current Biology.

[12]  Michael W Young,et al.  Regulation of Nuclear Entry of the Drosophila Clock Proteins Period and Timeless , 1996, Neuron.

[13]  M. Rosbash,et al.  A new gene encoding a putative transcription factor regulated by the Drosophila circadian clock , 1997, The EMBO journal.

[14]  Jeffrey C. Hall,et al.  A Mutant Drosophila Homolog of Mammalian Clock Disrupts Circadian Rhythms and Transcription of period and timeless , 1998, Cell.

[15]  M. W. Young,et al.  double-time Is a Novel Drosophila Clock Gene that Regulates PERIOD Protein Accumulation , 1998, Cell.

[16]  Jeffrey C. Hall,et al.  Evidence that the TIM Light Response Is Relevant to Light-Induced Phase Shifts in Drosophila melanogaster , 1998, Neuron.

[17]  J. C. Hall,et al.  Analysis of temperature-sensitive mutants reveals new genes involved in the courtship song of Drosophila. , 1998, Genetics.

[18]  I. Levitan,et al.  Slob, a Novel Protein that Interacts with the Slowpoke Calcium-Dependent Potassium Channel , 1998, Neuron.

[19]  W. Neckameyer Dopamine and mushroom bodies in Drosophila: experience-dependent and -independent aspects of sexual behavior. , 1998, Learning & memory.

[20]  R. Feyereisen Insect P450 enzymes. , 1999, Annual review of entomology.

[21]  R. Cooper,et al.  Dopaminergic modulation of motor neuron activity and neuromuscular function in Drosophila melanogaster. , 1999, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[22]  G. Hasan,et al.  Preferential Expression of Biotransformation Enzymes in the Olfactory Organs of Drosophila melanogaster, the Antennae* , 1999, The Journal of Biological Chemistry.

[23]  Paul E. Hardin,et al.  Circadian rhythms in olfactory responses of Drosophila melanogaster , 1999, Nature.

[24]  Michael W Young,et al.  Cycling vrille Expression Is Required for a Functional Drosophila Clock , 1999, Cell.

[25]  I. Levitan,et al.  A Dynamically Regulated 14–3–3, Slob, and Slowpoke Potassium Channel Complex in Drosophila Presynaptic Nerve Terminals , 1999, Neuron.

[26]  J. Hirsh,et al.  Circadian modulation of dopamine receptor responsiveness in Drosophila melanogaster. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[27]  M. Rosbash,et al.  The Drosophila takeout Gene Is a Novel Molecular Link between Circadian Rhythms and Feeding Behavior , 2000, Cell.

[28]  S. Ryter,et al.  The heme synthesis and degradation pathways: role in oxidant sensitivity. Heme oxygenase has both pro- and antioxidant properties. , 2000, Free radical biology & medicine.

[29]  J. L. Larimer,et al.  Molecular Separation of Two Behavioral Phenotypes by a Mutation Affecting the Promoters of a Ca-Activated K Channel , 2000, The Journal of Neuroscience.

[30]  Anthony Hall,et al.  The ELF3 zeitnehmer regulates light signalling to the circadian clock , 2000, Nature.

[31]  S. Kay,et al.  Orchestrated transcription of key pathways in Arabidopsis by the circadian clock. , 2000, Science.

[32]  F. Fleury-Olela,et al.  Analysis of circadian liver gene expression by ADDER, a highly sensitive method for the display of differentially expressed mRNAs. , 2001, Nucleic acids research.

[33]  S. Kay,et al.  Time zones: a comparative genetics of circadian clocks , 2001, Nature Reviews Genetics.

[34]  Adam Claridge‐Chang,et al.  Circadian Regulation of Gene Expression Systems in the Drosophila Head , 2001, Neuron.

[35]  Drosophila immunity: two paths to NF-kappaB. , 2001, Trends in immunology.

[36]  A. Sehgal,et al.  Role of Molecular Oscillations in Generating Behavioral Rhythms in Drosophila , 2001, Neuron.

[37]  A. J. Schroeder,et al.  A timely expression profile. , 2001, Developmental cell.

[38]  Michael J. McDonald,et al.  Microarray Analysis and Organization of Circadian Gene Expression in Drosophila , 2001, Cell.

[39]  Paul T. Spellman,et al.  Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[40]  B. Lemaître,et al.  Drosophila immunity: two paths to NF-κB , 2001 .

[41]  H. Ueda,et al.  Genome-wide Transcriptional Orchestration of Circadian Rhythms inDrosophila * 210 , 2002, The Journal of Biological Chemistry.

[42]  S. Kay,et al.  A P Element with a Novel Fusion of Reporters Identifies regular, a C2H2 Zinc-Finger Gene Downstream of the Circadian Clock , 2002, Molecular and Cellular Neuroscience.

[43]  Kai-Florian Storch,et al.  Extensive and divergent circadian gene expression in liver and heart , 2002, Nature.

[44]  Jeffrey C. Hall,et al.  Identification of circadian-clock-regulated enhancers and genes of Drosophila melanogaster by transposon mobilization and luciferase reporting of cyclical gene expression. , 2002, Genetics.

[45]  B. H. Miller,et al.  Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock , 2002, Cell.

[46]  M. Gho,et al.  Two distinct calcium-activated potassium currents in larval muscle fibres ofDrosophila melanogaster , 1986, Pflügers Archiv.