Interconnected feedback loops in the Neurospora circadian system.

@article{Lee2000InterconnectedFL,
  title={Interconnected feedback loops in the Neurospora circadian system.},
  author={K Lee and Jennifer J. Loros and Jay C. Dunlap},
  journal={Science},
  year={2000},
  volume={289 5476},
  pages={
          107-10
        }
}
In Neurospora crassa, white collar 1 (WC-1), a transcriptional activator and positive clock element, is rhythmically expressed from a nonrhythmic steady-state pool of wc-1 transcript, consistent with posttranscriptional regulation of rhythmicity. Mutations in frq influence both the level and periodicity of WC-1 expression, and driven FRQ expression not only depresses its own endogenous levels, but positively regulates WC-1 synthesis with a lag of about 8 hours, a delay similar to that seen in… 

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A new model for the Neurospora crassa circadian clock is proposed and it is demonstrated that explicit time delays are not required for sustained oscillations but that it is crucial to take into account mRNA dynamics and protein-protein interactions.

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This dissertation has taken a microarray approach to first determine the extent of clock-controlled gene expression in Neurospora, and shows that the FRQ/WC oscillator regulates rhythmic behavior and gene expression.

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Evidence from Neurospora crassa is reviewed that suggests that the circadian clock is organized as a network of genes and proteins that form coupled evening- and morning-specific oscillatory loops that can function autonomously, respond differently to environmental inputs, and regulate phase-specific outputs.

Simulating dark expressions and interactions of frq and wc-1 in the Neurospora circadian clock.

A model for the Neurospora circadian clock is constructed that suggests that even small amounts of nuclear FRQ-protein are capable of inhibiting frq transcription in a rhythmic manner by binding to WC-1 and promoting its degradation.
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References

SHOWING 1-10 OF 27 REFERENCES

Negative feedback defining a circadian clock: autoregulation of the clock gene frequency.

The frequency (frq) locus of Neurospora crassa is shown to encode a central component in a molecular feedback loop in which the product of frq negatively regulated its own transcript, which resulted in a daily oscillation in the amount offrq transcript.

Assignment of circadian function for the Neurospora clock gene frequency

Traditional circadian entrainment protocols are used to distinguish between under- or overexpression of a gene product can result in arrhythmicity, whether the protein is part of the oscillator or substantially part of a rhythmically expressed input pathway.

Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim.

The Drosophila CLOCK protein was shown to induce transcription of the circadian rhythm genes period and timeless, and PERIOD and TIMELESS proteins blocked dCLOCK's ability to transactivate their promoters via the E-box.

Role of the CLOCK protein in the mammalian circadian mechanism.

CLOCK-BMAL1 heterodimers appear to drive the positive component of per transcriptional oscillations, which are thought to underlie circadian rhythmicity.

Nuclear localization is required for function of the essential clock protein FRQ

It is reported that FRQ is a nuclear protein and nuclear localization is essential for its function, andKinetics of the nuclear entry are consistent with previous data showing rapid depression of frq transcript levels following the synthesis of FRQ, and suggest that early in each circadian cycle, it enters the nucleus and depresses the level of its own transcript.