TY - JOUR
T1 - Circadian yin-yang regulation and its manipulation to globally reprogram gene expression
AU - Xu, Yao
AU - Weyman, Philip D.
AU - Umetani, Miki
AU - Xiong, Jing
AU - Qin, Ximing
AU - Xu, Qing
AU - Iwasaki, Hideo
AU - Johnson, Carl Hirschie
N1 - Funding Information:
We are grateful to our colleagues at Vanderbilt for valuable discussions, especially Jamey Young, Tetsuya Mori, and Brian Robertson, and to Walter A. Vargas for technical assistance. We thank Susan Golden for the gifts of the neutral site vectors and luminescence reporter plasmids psbAI p:: luxAB and fis p:: luxAB , Shinsuke Kutsuna for the kaiA overexpression constructs in NS II, Peter Greenberg for the antibody to bacterial luciferase, and Tetsuya Mori for ftsZ p:: luxAB DNA. This research was supported by grants from National Institute of General Medical Sciences (NIGMS R01 GM067152 and R01 GM088595 to C.H.J.); the Hydrogen, Fuel Cells, and Infrastructure Technology Program of the US Department of Energy (DE-FG36-05GO15027 to P.D.W. and Q.X.); the Japanese Society for the Promotion of Science (23657138 and 23687002) and the Asahi Glass Foundation to H.I.; and the Yoshida Scholarship Foundation to M.U.
PY - 2013/12/2
Y1 - 2013/12/2
N2 - 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 "subjective dusk" 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 "yin-yang" regulation of gene expression whereby kaiA overexpression activates "dusk genes" and represses "dawn genes," 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.
AB - 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 "subjective dusk" 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 "yin-yang" regulation of gene expression whereby kaiA overexpression activates "dusk genes" and represses "dawn genes," 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.
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U2 - 10.1016/j.cub.2013.10.011
DO - 10.1016/j.cub.2013.10.011
M3 - Article
C2 - 24210617
AN - SCOPUS:84889591546
VL - 23
SP - 2365
EP - 2374
JO - Current Biology
JF - Current Biology
SN - 0960-9822
IS - 23
ER -