title: vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock.
abstract: The Drosophila circadian clock consists of two interlocked transcriptional feedback loops. In one loop, dCLOCK/CYCLE activates period expression, and PERIOD protein then inhibits dCLOCK/CYCLE activity. dClock is also rhythmically transcribed, but its regulators are unknown. vrille (vri) and Par Domain Protein 1 (Pdp1) encode related transcription factors whose expression is directly activated by dCLOCK/CYCLE. We show here that VRI and PDP1 proteins feed back and directly regulate dClock expression. Repression of dClock by VRI is separated from activation by PDP1 since VRI levels peak 3-6 hours before PDP1. Rhythmic vri transcription is required for molecular rhythms, and here we show that the clock stops in a Pdp1 null mutant, identifying Pdp1 as an essential clock gene. Thus, VRI and PDP1, together with dClock itself, comprise a second feedback loop in the Drosophila clock that gives rhythmic expression of dClock, and probably of other genes, to generate accurate circadian rhythms.
authors.affiliation: Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA.
authors.forename: Shawn A
authors.initials: SA
authors.lastname: Cyran
authors.forename: Anna M
authors.initials: AM
authors.lastname: Buchsbaum
authors.forename: Karen L
authors.initials: KL
authors.lastname: Reddy
authors.forename: Meng-Chi
authors.initials: MC
authors.lastname: Lin
authors.forename: Nicholas R J
authors.initials: NR
authors.lastname: Glossop
authors.forename: Paul E
authors.initials: PE
authors.lastname: Hardin
authors.forename: Michael W
authors.initials: MW
authors.lastname: Young
authors.forename: Robert V
authors.initials: RV
authors.lastname: Storti
authors.forename: Justin
authors.initials: J
authors.lastname: Blau
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D001522:Behavior, Animal / Q000502:physiology; D001683:Biological Clocks / Q000235:genetics*; D056926:CLOCK Proteins; D002940:Circadian Rhythm / Q000235:genetics*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D005246:Feedback / Q000502:physiology*; D005260:Female; D008297:Male; D009154:Mutation / Q000235:genetics; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C120526:Clk protein, Drosophila; D029721:Drosophila Proteins; C109768:PDP1 protein, Drosophila; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C108498:vri protein, Drosophila; D056926:CLOCK Proteins