Circadian Yin-Yang Regulation and Its Manipulation to Globally Reprogram Gene Expression

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• 作者：Yao Xu ; Philip聽D. Weyman ; Miki Umetani ; Jing Xiong ; Ximing Qin ; Qing Xu ; Hideo Iwasaki ; Carl聽Hirschie Johnson
• 刊名：Current Biology
• 出版年：2 December, 2013
• 年：2013
• 卷：23
• 期：23
• 页码：2365-2374
• 全文大小：2272 K

文摘

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Summary

Background

The cyanobacterial circadian program exerts genome-wide control of gene expression. KaiC undergoes rhythms of phosphorylation that are regulated by interactions with KaiA and KaiB. The phosphorylation status of KaiC is thought to mediate global transcription via output factors SasA, CikA, LabA, RpaA, and RpaB. Overexpression of kaiC has been reported to globally repress gene expression.

Results

Here, we show that the positive circadian component KaiA upregulates 鈥渟ubjective dusk鈥?genes and that its overexpression deactivates rhythmic gene expression without significantly affecting growth rates in constant light. We analyze the global patterns of expression that are regulated by KaiA versus KaiC and find in contrast to the previous report of KaiC repression that there is a 鈥測in-yang鈥?regulation of gene expression whereby kaiA overexpression activates 鈥渄usk genes鈥?and represses 鈥渄awn genes,鈥?whereas kaiC overexpression complementarily activates dawn genes and represses dusk genes. Moreover, continuous induction of kaiA latched KaiABC-regulated gene expression to provide constitutively increased transcript levels of diverse endogenous and heterologous genes that are expressed in the predominant subjective dusk phase. In addition to analyzing KaiA regulation of endogenous gene expression, we apply these insights to the expression of heterologous proteins whose products are of potential value, namely human proinsulin, foreign luciferase, and exogenous hydrogenase.

Conclusions

Both KaiC and KaiA complementarily contribute to the regulation of circadian gene expression via yin-yang switching. Circadian patterns can be reprogrammed by overexpression of kaiA or kaiC to constitutively enhance gene expression, and this reprogramming can improve 24/7 production of heterologous proteins that are useful as pharmaceuticals or biofuels.