ArticlePLoS computational biology2013
Revealing a two-loop transcriptional feedback mechanism in the cyanobacterial circadian clock.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 16 citations in OpenAlex.
- Damped circadian oscillation in the absence of KaiA in Synechococcus.Nature communications · 2020Article
- Article
- Computational modelling unravels the precise clockwork of cyanobacteria.Interface focus · 2018Review
- Toward Multiscale Models of Cyanobacterial Growth: A Modular Approach.Frontiers in bioengineering and biotechnology · 2016Review
- Daily expression pattern of protein-encoding genes and small noncoding RNAs in synechocystis sp. strain PCC 6803.Applied and environmental microbiology · 2014Article
- Insight into cyanobacterial circadian timing from structural details of the KaiB-KaiC interaction.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular genetic studies in the circadian model organism Synechococcus have revealed that the KaiC protein, the central component of the circadian clock in cyanobacteria, is involved in activation and repression of its own gene transcription. During 24 hours, KaiC hexamers run through different phospho-states during daytime. So far, it has remained unclear which phospho-state of KaiC promotes kaiBC expression and which opposes transcriptional activation. We systematically analyzed various combinations of positive and negative transcriptional feedback regulation by introducing a combined TTFL/PTO model consisting of our previous post-translational oscillator that considers all four phospho-states of KaiC and a transcriptional/translational feedback loop. Only a particular two-loop feedback mechanism out of 32 we have extensively tested is able to reproduce existing experimental observations, including the effects of knockout or overexpression of kai genes. Here, threonine and double phosphorylated KaiC hexamers activate and unphosphorylated KaiC hexamers suppress kaiBC transcription. Our model simulations suggest that the peak expression ratio of the positive and the negative component of kaiBC expression is the main factor for how the different two-loop feedback models respond to removal or to overexpression of kai genes. We discuss parallels between our proposed TTFL/PTO model and two-loop feedback structures found in the mammalian clock.
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