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

vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock
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DOI:
10.1016/s0092-8674(03)00074-6
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发表时间:
2003-02-07
期刊:
影响因子:
64.5
通讯作者:
Blau, J
Blau, J
中科院分区:
生物学1区
文献类型:
--
作者:
Cyran, SA;Buchsbaum, AM;Blau, J

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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.