Interconnected feedback loops in the Neurospora circadian system.

  title={Interconnected feedback loops in the Neurospora circadian system.},
  author={K Lee and Jennifer J. Loros and Jay C. Dunlap},
  volume={289 5476},
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… 

A model for the Neurospora circadian clock.

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.

Control of rhythmic output from the circadian clock in Neurospora crassa

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.

Interlocked feedback loops contribute to the robustness of the Neurospora circadian clock

The data demonstrate that the greater the levels of WC-1 and WC-2, the higher the level of the FRQ oscillation and the more robust the overt rhythms, suggesting that the interlocked circadian feedback loops are also important for determining the circadian period length of the clock.

The Neurospora Circadian System

Overall, the FRQ/white collar complex feedback loop appears to coordinate the circadian system through its activity to regulate downstream-target clock-controlled genes, either directly or via regulation of driven FLOs.

Two Circadian Timing Circuits in Neurospora crassa Cells Share Components and Regulate Distinct Rhythmic Processes

Evidence is provided that the FLO driving ccg-16 rhythmicity is a circadian oscillator, and the results are consistent with the presence of 2 circadian oscillators within Neurospora cells, which the authors speculate may interact with each other through the shared WC proteins.

Reduced models of the circadian oscillators in Neurospora crassa and Drosophila melanogaster illustrate mechanistic similarities.

Simulations suggest that in both Neurospora and Drosophila, only the negative feedback loop is essential for circadian oscillations, which may aid understanding of circadian mechanisms in mammals and other organisms.

Interlocked feedback loops of the circadian clock of Neurospora crassa

This review summarizes the knowledge of the molecular basis of circadian time keeping in Neurospora and discusses the mechanisms by which environmental cues like light and temperature entrain and reset this circadian system.

Complexity of the Neurospora crassa circadian clock system: multiple loops and oscillators.

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.



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.