title: Frequency doubling in the cyanobacterial circadian clock.
abstract: Organisms use circadian clocks to generate 24-h rhythms in gene expression. However, the clock can interact with other pathways to generate shorter period oscillations. It remains unclear how these different frequencies are generated. Here, we examine this problem by studying the coupling of the clock to the alternative sigma factor sigC in the cyanobacterium Synechococcus elongatus Using single-cell microscopy, we find that psbAI, a key photosynthesis gene regulated by both sigC and the clock, is activated with two peaks of gene expression every circadian cycle under constant low light. This two-peak oscillation is dependent on sigC, without which psbAI rhythms revert to one oscillatory peak per day. We also observe two circadian peaks of elongation rate, which are dependent on sigC, suggesting a role for the frequency doubling in modulating growth. We propose that the two-peak rhythm in psbAI expression is generated by an incoherent feedforward loop between the clock, sigC and psbAI Modelling and experiments suggest that this could be a general network motif to allow frequency doubling of outputs.
authors.affiliation: Sainsbury Laboratory, University of Cambridge, Cambridge, UK.
authors.forename: Bruno Mc
authors.initials: BM
authors.lastname: Martins
authors.affiliation: Sainsbury Laboratory, University of Cambridge, Cambridge, UK.
authors.forename: Arijit K
authors.initials: AK
authors.lastname: Das
authors.affiliation: Sainsbury Laboratory, University of Cambridge, Cambridge, UK.|Wellcome Trust Sanger Institute Wellcome Trust Genome Campus, Hinxton Cambridge, UK.
authors.forename: Liliana
authors.initials: L
authors.lastname: Antunes
authors.affiliation: Sainsbury Laboratory, University of Cambridge, Cambridge, UK james.locke@slcu.cam.ac.uk.|Department of Biochemistry, University of Cambridge, Cambridge, UK.|Microsoft Research, Cambridge, UK.
authors.forename: James Cw
authors.identifier: http://orcid.org/0000-0003-0670-1943
authors.initials: JC
authors.lastname: Locke
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D057906:Circadian Clocks; D015964:Gene Expression Regulation, Bacterial; D008954:Models, Biological; D057054:Molecular Imaging; D010788:Photosynthesis; D045332:Photosystem II Protein Complex / Q000378:metabolism*; D012808:Sigma Factor / Q000378:metabolism*; D059010:Single-Cell Analysis; D046940:Synechococcus / Q000502:physiology*; D059008:Time-Lapse Imaging
chemical_list: D001426:Bacterial Proteins; D045332:Photosystem II Protein Complex; D012808:Sigma Factor
keywords: circadian clock; cyanobacteria; mathematical modelling; network motifs; single‐cell time‐lapse microscopy