Identification of novel light-induced genes in the suprachiasmatic nucleus

BackgroundThe transmission of information about the photic environment to the circadian clock involves a complex array of neurotransmitters, receptors, and second messenger systems. Exposure of an animal to light during the subjective night initiates rapid transcription of a number of immediate-early genes in the suprachiasmatic nucleus of the hypothalamus. Some of these genes have known roles in entraining the circadian clock, while others have unknown functions. Using laser capture microscopy, microarray analysis, and quantitative real-time PCR, we performed a comprehensive screen for changes in gene expression immediately following a 30 minute light pulse in suprachiasmatic nucleus of mice.ResultsThe results of the microarray screen successfully identified previously known light-induced genes as well as several novel genes that may be important in the circadian clock. Newly identified light-induced genes include early growth response 2, proviral integration site 3, growth-arrest and DNA-damage-inducible 45 beta, and TCDD-inducible poly(ADP-ribose) polymerase. Comparative analysis of promoter sequences revealed the presence of evolutionarily conserved CRE and associated TATA box elements in most of the light-induced genes, while other core clock genes generally lack this combination of promoter elements.ConclusionThe photic signalling cascade in the suprachiasmatic nucleus activates an array of immediate-early genes, most of which have unknown functions in the circadian clock. Detected evolutionary conservation of CRE and TATA box elements in promoters of light-induced genes suggest that the functional role of these elements has likely remained the same over evolutionary time across mammalian orders.

[1]  P. Sassone-Corsi,et al.  Light-Inducible and Clock-Controlled Expression of MAP Kinase Phosphatase 1 in Mouse Central Pacemaker Neurons , 2007, Journal of biological rhythms.

[2]  C. Grimm,et al.  Light-induced cell death of retinal photoreceptors in the absence of p53. , 1998, Investigative ophthalmology & visual science.

[3]  K. Fukunaga,et al.  Involvement of calcium/calmodulin‐dependent protein kinase II in the induction of mPer1 , 2003, Journal of neuroscience research.

[4]  L. A. Stargell,et al.  Non-optimal TATA Elements Exhibit Diverse Mechanistic Consequences* , 2006, Journal of Biological Chemistry.

[5]  Mark J. Zylka,et al.  Two period Homologs: Circadian Expression and Photic Regulation in the Suprachiasmatic Nuclei , 1997, Neuron.

[6]  B. Hoffman,et al.  Gadd45a and Gadd45b Protect Hematopoietic Cells from UV-induced Apoptosis via Distinct Signaling Pathways, including p38 Activation and JNK Inhibition* , 2006, Journal of Biological Chemistry.

[7]  R. Gibbs,et al.  PipMaker--a web server for aligning two genomic DNA sequences. , 2000, Genome research.

[8]  M. Levine,et al.  Glutamate receptor-induced toxicity in neostriatal cells , 1996, Brain Research.

[9]  T. Werner,et al.  MatInd and MatInspector: new fast and versatile tools for detection of consensus matches in nucleotide sequence data. , 1995, Nucleic acids research.

[10]  J. Touchman,et al.  Vertebrate genome sequencing: building a backbone for comparative genomics. , 2002, Trends in genetics : TIG.

[11]  Masaki Tanaka,et al.  Induction of NGFI-A gene expression in the rat suprachiasmatic nucleus by photic stimulation , 1997, Brain Research.

[12]  Greg Q. Butcher,et al.  The ERK/MAP kinase pathway couples light to immediate‐early gene expression in the suprachiasmatic nucleus , 2003, The European journal of neuroscience.

[13]  R. Fukumura,et al.  Identification of genes that express in response to light exposure and express rhythmically in a circadian manner in the mouse suprachiasmatic nucleus , 2006, Brain Research.

[14]  Rae Silver,et al.  Orchestrating time: arrangements of the brain circadian clock , 2005, Trends in Neurosciences.

[15]  N. Billestrup,et al.  Growth arrest- and DNA-damage-inducible 45β gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1β-induced apoptosis in insulin-producing INS-1E cells , 2006, Diabetologia.

[16]  Sudhir Kumar,et al.  Genomic clocks and evolutionary timescales. , 2003, Trends in genetics : TIG.

[17]  C. Colwell,et al.  Phase-shifting mechanisms in the mammalian circadian system: new light on the carbachol paradox , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  W. Schwartz,et al.  Photoperiod-dependent correlation between light-induced SCN c-fos expression and resetting of circadian phase. , 1996, The American journal of physiology.

[19]  Boyoung Lee,et al.  Light Stimulates MSK1 Activation in the Suprachiasmatic Nucleus via a PACAP-ERK/MAP Kinase-Dependent Mechanism , 2005, The Journal of Neuroscience.

[20]  J. Kornhauser,et al.  Visual sensitivities of nur77 (NGFI-B) and zif268 (NGFI-A) induction in the suprachiasmatic nucleus are dissociated from c-fos induction and behavioral phase-shifting responses. , 1997, Brain research. Molecular brain research.

[21]  W. Schwartz,et al.  Unexpected c-fos Gene Expression in the Suprachiasmatic Nucleus of Mice Entrained to a Skeleton Photoperiod , 1996, Journal of biological rhythms.

[22]  K. Fukunaga,et al.  MAP kinase additively activates the mouse Per1 gene promoter with CaM kinase II , 2006, Brain Research.

[23]  M. Mukai,et al.  Effects of tryptophan photoproducts in the circadian timing system: searching for a physiological role for aryl hydrocarbon receptor. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[24]  Andrew I Su,et al.  Genome-wide analysis of CREB target genes reveals a core promoter requirement for cAMP responsiveness. , 2003, Molecular cell.

[25]  L. A. Stargell,et al.  The Stability of the TFIIA-TBP-DNA Complex Is Dependent on the Sequence of the TATAAA Element* , 2001, The Journal of Biological Chemistry.

[26]  N. M. Brooke,et al.  A molecular timescale for vertebrate evolution , 1998, Nature.

[27]  K. Tsuneyama,et al.  Proto‐oncogene, Pim‐3 with serine/threonine kinase activity, is aberrantly expressed in human colon cancer cells and can prevent Bad‐mediated apoptosis , 2007, Cancer science.

[28]  J. Kornhauser,et al.  Light, immediate-early genes, and circadian rhythms , 1996, Behavior genetics.

[29]  Boyoung Lee,et al.  Temporal regulation of light-induced extracellular signal-regulated kinase activation in the suprachiasmatic nucleus. , 2003, Journal of neurophysiology.

[30]  I-Min A. Dubchak,et al.  Active conservation of noncoding sequences revealed by three-way species comparisons. , 2000, Genome research.

[31]  Q. Ma Induction and superinduction of 2,3,7,8-tetrachlorodibenzo-rho-dioxin-inducible poly(ADP-ribose) polymerase: role of the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator transcription activation domains and a labile transcription repressor. , 2002, Archives of biochemistry and biophysics.

[32]  I. Lim,et al.  TIS21/BTG2/PC3 as a link between ageing and cancer: cell cycle regulator and endogenous cell death molecule , 2006, Journal of Cancer Research and Clinical Oncology.

[33]  D. Haussler,et al.  Human-mouse alignments with BLASTZ. , 2003, Genome research.

[34]  R. Duman,et al.  Electroconvulsive seizure‐induced gene expression profile of the hippocampus dentate gyrus granule cell layer , 2006, Journal of neurochemistry.

[35]  D. Storm,et al.  Circadian Regulation of cAMP Response Element-mediated Gene Expression in the Suprachiasmatic Nuclei* , 1999, The Journal of Biological Chemistry.

[36]  Lily Yan,et al.  Light-Induced Resetting of a Mammalian Circadian Clock Is Associated with Rapid Induction of the mPer1 Transcript , 1997, Cell.

[37]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[38]  D. Peeper,et al.  KLF4, p21 and context-dependent opposing forces in cancer , 2006, Nature Reviews Cancer.

[39]  Hiroshi Ishikura,et al.  Pim-3, a proto-oncogene with serine/threonine kinase activity, is aberrantly expressed in human pancreatic cancer and phosphorylates bad to block bad-mediated apoptosis in human pancreatic cancer cell lines. , 2006, Cancer research.

[40]  M. Gillette,et al.  Response Element-binding Protein ( CREB )-dependent Activation of Per 1 Is Required for Light-induced Signaling in the Suprachiasmatic Nucleus Circadian Clock , 2002 .

[41]  Thomas Werner,et al.  MatInspector and beyond: promoter analysis based on transcription factor binding sites , 2005, Bioinform..

[42]  K. Schlingensiepen,et al.  Block of c‐Fos and JunB Expression by Antisense Oligonucleotides Inhibits Light‐induced‐Phase Shifts of the Mammalian Circadian Clock , 1995, The European journal of neuroscience.

[43]  S. Kuhlman,et al.  A screen for genes induced in the suprachiasmatic nucleus by light. , 1998, Science.

[44]  Mei Li,et al.  MultiPipMaker and supporting tools: alignments and analysis of multiple genomic DNA sequences , 2003, Nucleic Acids Res..

[45]  H. Heller,et al.  Characterization of the Circadian System of NGFI-A and NGFI-A/NGFI-B Deficient Mice , 1998, Journal of biological rhythms.

[46]  Pierre Baldi,et al.  A Bayesian framework for the analysis of microarray expression data: regularized t -test and statistical inferences of gene changes , 2001, Bioinform..

[47]  J. Hogenesch,et al.  Characterization of a Subset of the Basic-Helix-Loop-Helix-PAS Superfamily That Interacts with Components of the Dioxin Signaling Pathway* , 1997, The Journal of Biological Chemistry.

[48]  Yuichiro Yamada,et al.  Nuclear sequestration of beta-subunits by Rad and Rem is controlled by 14-3-3 and calmodulin and reveals a novel mechanism for Ca2+ channel regulation. , 2006, Journal of molecular biology.

[49]  B. Spiegelman,et al.  The circadian system of c-fos deficient mice , 1996, Journal of Comparative Physiology A.

[50]  N. Mrosovsky,et al.  Behavioral arousal blocks light-induced phase advances in locomotor rhythmicity but not light-induced Per1 and Fos expression in the hamster suprachiasmatic nucleus , 2003, Neuroscience.

[51]  Andreas Prlic,et al.  Ensembl 2007 , 2006, Nucleic Acids Res..

[52]  Boyoung Lee,et al.  Light Stimulates MSK 1 Activation in the Suprachiasmatic Nucleus via a PACAP-ERK / MAP Kinase-Dependent Mechanism , 2005 .

[53]  C. Kahn,et al.  Rad and Rad-related GTPases Interact with Calmodulin and Calmodulin-dependent Protein Kinase II* , 1997, The Journal of Biological Chemistry.

[54]  Paolo Sassone-Corsi,et al.  Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity , 2002, Proceedings of the National Academy of Sciences of the United States of America.