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

Autor: Paul E. Hardin, Karen L. Reddy, Justin Blau, Meng Chi Lin, Michael W. Young, Anna M. Buchsbaum, Nicholas R J Glossop, Robert V. Storti, Shawn A. Cyran
Rok vydání: 2003
Předmět:
Zdroj: Cell. 112(3)
ISSN: 0092-8674
Popis: 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.
Databáze: OpenAIRE