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

Cell. 2003 Feb 7;112(3):329-41. doi: 10.1016/s0092-8674(03)00074-6.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Comment

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors
  • Behavior, Animal / physiology
  • Biological Clocks / genetics*
  • CLOCK Proteins
  • Circadian Rhythm / genetics*
  • Drosophila Proteins*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Feedback / physiology*
  • Female
  • Male
  • Mutation / genetics
  • Photoreceptor Cells, Invertebrate / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation / genetics

Substances

  • Basic-Leucine Zipper Transcription Factors
  • Clk protein, Drosophila
  • Drosophila Proteins
  • PDP1 protein, Drosophila
  • RNA, Messenger
  • Repressor Proteins
  • Transcription Factors
  • vri protein, Drosophila
  • CLOCK Proteins