Circadian Control of Global Gene Expression by the Cyanobacterial Master Regulator RpaA

•RpaA is required for transmission of time from the core oscillator to clock outputs•rpaA deletion arrests cells in a dawn-like state, with no circadian gene expression•RpaA binds to 110 sites and activates global regulators such as sigma factors•Overexpression of activated RpaA switches cells from dawn to dusk state

SummaryThe cyanobacterial circadian clock generates genome-wide transcriptional oscillations and regulates cell division, but the underlying mechanisms are not well understood. Here, we show that the response regulator RpaA serves as the master regulator of these clock outputs. Deletion of rpaA abrogates gene expression rhythms globally and arrests cells in a dawn-like expression state. Although rpaA deletion causes core oscillator failure by perturbing clock gene expression, rescuing oscillator function does not restore global expression rhythms. We show that phosphorylated RpaA regulates the expression of not only clock components, generating feedback on the core oscillator, but also a small set of circadian effectors that, in turn, orchestrate genome-wide transcriptional rhythms. Expression of constitutively active RpaA is sufficient to switch cells from a dawn-like to a dusk-like expression state as well as to block cell division. Hence, complex global circadian phenotypes can be generated by controlling the phosphorylation of a single transcription factor.

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