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Design of synthetic epigenetic circuits featuring memory effects and reversible switching based on DNA methylation

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  • Johannes A. H. Maier

    (Institute of Biochemistry, Faculty of Chemistry, Stuttgart University)

  • Raphael Möhrle

    (Institute of Biochemistry, Faculty of Chemistry, Stuttgart University)

  • Albert Jeltsch

    (Institute of Biochemistry, Faculty of Chemistry, Stuttgart University)

Abstract

Epigenetic systems store information in DNA methylation patterns in a durable but reversible manner, but have not been regularly used in synthetic biology. Here, we designed synthetic epigenetic memory systems using DNA methylation sensitive engineered zinc finger proteins to repress a memory operon comprising the CcrM methyltransferase and a reporter. Triggering by heat, nutrients, ultraviolet irradiation or DNA damaging compounds induces CcrM expression and DNA methylation. In the induced on-state, methylation in the operator of the memory operon prevents zinc finger protein binding leading to positive feedback and permanent activation. Using an mf-Lon protease degradable CcrM variant enables reversible switching. Epigenetic memory systems have numerous potential applications in synthetic biology, including life biosensors, death switches or induction systems for industrial protein production. The large variety of bacterial DNA methyltransferases potentially allows for massive multiplexing of signal storage and logical operations depending on more than one input signal.

Suggested Citation

  • Johannes A. H. Maier & Raphael Möhrle & Albert Jeltsch, 2017. "Design of synthetic epigenetic circuits featuring memory effects and reversible switching based on DNA methylation," Nature Communications, Nature, vol. 8(1), pages 1-10, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15336
    DOI: 10.1038/ncomms15336
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