labA: a novel gene required for negative feedback regulation of the cyanobacterial circadian clock protein KaiC.
In the cyanobacterium Synechococcus elongatus PCC 7942, circadian timing is transmitted from the KaiABC-based central oscillator to the transcription factor RpaA via the KaiC-interacting histidine kinase SasA to activate transcription, thereby generating rhythmic circadian gene expression. However, KaiC can also repress circadian gene expression, including its own. The mechanism and significance of this negative feedback regulation have been unclear. Here, we report a novel gene, labA (low-amplitude and bright), that is required for negative feedback regulation of KaiC. Disruption of labA abolished transcriptional repression caused by overexpression of KaiC and elevated the trough levels of circadian gene expression, resulting in a low-amplitude phenotype. In contrast, overexpression of labA significantly lowered circadian gene expression. Furthermore, genetic analysis indicated that labA and sasA function in parallel pathways to regulate kaiBC expression, whereas rpaA functions downstream from labA for kaiBC expression. These results suggest that temporal information from the KaiABC-based oscillator diverges into a LabA-dependent negative pathway and a SasA-dependent positive pathway, and then converges onto RpaA to generate robust circadian gene expression. It is likely that quantitative information of KaiC is transmitted to RpaA through LabA, whereas SasA mediates the state of the KaiABC-based oscillator.
Taniguchi
Yasuhito
Y
Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan.
Katayama
Mitsunori
M
Ito
Rie
R
Takai
Naoki
N
Kondo
Takao
T
Oyama
Tokitaka
T
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001483:Base Sequence; D001683:Biological Clocks / Q000235:genetics*; D015152:Blotting, Northern; D015153:Blotting, Western; D002940:Circadian Rhythm / Q000502:physiology*; D056925:Circadian Rhythm Signaling Peptides and Proteins; D025461:Feedback, Physiological / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D046940:Synechococcus / Q000502:physiology*; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D056925:Circadian Rhythm Signaling Peptides and Proteins; C114269:KaiA protein, cyanobacteria; C114270:KaiB protein, cyanobacteria; C114271:KaiC protein, cyanobacteria; D012097:Repressor Proteins; D010770:Phosphotransferases; C083143:SasA protein, Synechococcus