Systems Biology of the Clock in Neurospora crassa

Abstract

A model-driven discovery process, Computing Life, is used to identify an ensemble of genetic networks that describe the biological clock. A clock mechanism involving the genes white-collar-1 and white-collar-2 (wc-1 and wc-2) that encode a transcriptional activator (as well as a blue-light receptor) and an oscillator frequency (frq) that encodes a cyclin that deactivates the activator is used to guide this discovery process through three cycles of microarray experiments. Central to this discovery process is a new methodology for the rational design of a Maximally Informative Next Experiment (MINE), based on the genetic network ensemble. In each experimentation cycle, the MINE approach is used to select the most informative new experiment in order to mine for clock-controlled genes, the outputs of the clock. As much as 25% of the N. crassa transcriptome appears to be under clock-control. Clock outputs include genes with products in DNA metabolism, ribosome biogenesis in RNA metabolism, cell cycle, protein metabolism, transport, carbon metabolism, isoprenoid (including carotenoid) biosynthesis, development, and varied signaling processes. Genes under the transcription factor complex WCC ( = WC-1/WC-2) control were resolved into four classes, circadian only (612 genes), light-responsive only (396), both circadian and light-responsive (328), and neither circadian nor light-responsive (987). In each of three cycles of microarray experiments data support that wc-1 and wc-2 are auto-regulated by WCC. Among 11,000 N. crassa genes a total of 295 genes, including a large fraction of phosphatases/kinases, appear to be under the immediate control of the FRQ oscillator as validated by 4 independent microarray experiments. Ribosomal RNA processing and assembly rather than its transcription appears to be under clock control, suggesting a new mechanism for the post-transcriptional control of clock-controlled genes.

Regulation of Conidiation by Light in Aspergillus nidulans

“…changes in transcriptional levels of many different families of genes drive physiological and developmental changes (Dong et al 2008;Greenwald et al 2010). These changes in transcription were observed over a period of time broader than in our microarray experiment.…”

Dehydrogenase GRD1 Represents a Novel Component of the Cellulase Regulon in Trichoderma reesei (Hypocrea jecorina)

“…On one hand, light-dependent splicing has been shown in fungi (49,69), but if this mechanism were at work, additional bands resulting from (probably nonfunctional) truncated versions of CBH1 should have been detected on Western blots for light-grown cultures, which was not the case. However, clock regulation of ribosome biogenesis (but not transcriptional regulation of ribosome genes) has been shown and, hence, provides a means for posttranscriptional regulation of clock-controlled genes (11). Because of the crucial importance of light for resetting of the circadian clock, such a mechanism is likely to also be affected by light, which would provide a reasonable explanation for posttranscriptional regulation of cellulase gene expression by light.…”

The Genomes of Three Uneven Siblings: Footprints of the Lifestyles of Three Trichoderma Species

“…Consequently, these signaling systems have functions in stress response, fungicide resistance, and development. Interestingly, it was shown that several components of the N. crassa two-component phosphorelay system are clock controlled (730). According to the classification system established in reference 731, T. atroviride, T. virens, and T. reesei have histidine kinases belonging to classes I, II, III, IV, V, VI, VIII, IX, X, and XI (see Fig.…”