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vrille, Pdp1, and dClock Form a Second Feedback Loop in the Drosophila Circadian Clock
Ist Teil von
Cell, 2003-02, Vol.112 (3), p.329-341
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2003
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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.