vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock

Shawn A. Cyran, Anna M. Buchsbaum, Karen L. Reddy, Meng Chi Lin, Nicholas R J Glossop, Paul E. Hardin, Michael W. Young, Robert V. Storti, Justin Blau

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)329-341
Number of pages13
JournalCell
Volume112
Issue number3
DOIs
StatePublished - Feb 7 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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