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Revealing a Two-Loop Transcriptional Feedback Mechanism in the Cyanobacterial Circadian Clock

Figure 2

Four two-loop feedback models reproduce the effects of kaiA knockout mutants on kaiBC expression and KaiC phosphorylation.

Predicted time-series of kaiBC expression and KaiC phosphorylation in the absence of the kaiA gene. Deletion of the kaiA gene was simulated through setting the kaiA transcription rate to zero. Of the six models of Group I, which captured the measured kaiBC expression and KaiC phosphorylation dynamics, three models correctly reflect the effects of kaiA depletion as well: HTD+-HU− (A), HP+-HU− (B), and HTD+-HS− (C). Simulated deletion of kaiA transcription in these models destroys kaiBC gene expression and KaiC phosphorylation rhythm in parallel. The levels of kaiBC mRNA and PKaiC are reduced. These models were analyzed further in Figure 4. (D) Of the six models of Group II, only the HD+-BT− model correctly reflects the effects of kaiA depletion as well. This model, however, cannot reproduce upregulation of kaiBC expression upon overexpression of the kaiA gene (see Figure S9). The HU+-HT−, HS+-HD− and HT+-HS− models of Group I and the HT+-BU−, HD+-BU−, HP+-BU−, HU+-BP−, and HU+-BD− fail to recapitulate downregulation of kaiBC expression upon kaiA inactivation (Figure S7). The abbreviations are explained in Figure 1.

Figure 2

doi: https://doi.org/10.1371/journal.pcbi.1002966.g002