Circadian yin-yang regulation and its manipulation to globally reprogram gene expression

Yao Xu, Philip D. Weyman, Miki Umetani, Jing Xiong, Ximing Qin, Qing Xu, Hideo Iwasaki, Carl Hirschie Johnson

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)2365-2374
    Number of pages10
    JournalCurrent Biology
    Volume23
    Issue number23
    DOIs
    Publication statusPublished - 2013 Dec 2

    Fingerprint

    Yin-Yang
    Gene expression
    Genes
    Gene Expression
    gene expression
    Gene Expression Regulation
    genes
    Phosphorylation
    phosphorylation
    Hydrogenase
    proinsulin
    Proinsulin
    Biofuels
    Sasa
    Luciferases
    protein products
    gene expression regulation
    luciferase
    biofuels
    Proteins

    ASJC Scopus subject areas

    • Agricultural and Biological Sciences(all)
    • Biochemistry, Genetics and Molecular Biology(all)

    Cite this

    Xu, Y., Weyman, P. D., Umetani, M., Xiong, J., Qin, X., Xu, Q., ... Johnson, C. H. (2013). Circadian yin-yang regulation and its manipulation to globally reprogram gene expression. Current Biology, 23(23), 2365-2374. https://doi.org/10.1016/j.cub.2013.10.011

    Circadian yin-yang regulation and its manipulation to globally reprogram gene expression. / Xu, Yao; Weyman, Philip D.; Umetani, Miki; Xiong, Jing; Qin, Ximing; Xu, Qing; Iwasaki, Hideo; Johnson, Carl Hirschie.

    In: Current Biology, Vol. 23, No. 23, 02.12.2013, p. 2365-2374.

    Research output: Contribution to journalArticle

    Xu, Y, Weyman, PD, Umetani, M, Xiong, J, Qin, X, Xu, Q, Iwasaki, H & Johnson, CH 2013, 'Circadian yin-yang regulation and its manipulation to globally reprogram gene expression', Current Biology, vol. 23, no. 23, pp. 2365-2374. https://doi.org/10.1016/j.cub.2013.10.011
    Xu, Yao ; Weyman, Philip D. ; Umetani, Miki ; Xiong, Jing ; Qin, Ximing ; Xu, Qing ; Iwasaki, Hideo ; Johnson, Carl Hirschie. / Circadian yin-yang regulation and its manipulation to globally reprogram gene expression. In: Current Biology. 2013 ; Vol. 23, No. 23. pp. 2365-2374.
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    abstract = "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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    AU - Xiong, Jing

    AU - Qin, Ximing

    AU - Xu, Qing

    AU - Iwasaki, Hideo

    AU - Johnson, Carl Hirschie

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    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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