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Autor(en): Maier, Johannes A. H.
Möhrle, Raphael
Jeltsch, Albert
Titel: Design of synthetic epigenetic circuits featuring memory effects and reversible switching based on DNA methylation
Erscheinungsdatum: 2017
Dokumentart: Zeitschriftenartikel
Seiten: 10
Erschienen in: Nature communications 8 (2017), No. 15336
URI: http://elib.uni-stuttgart.de/handle/11682/9160
http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-91603
http://dx.doi.org/10.18419/opus-9143
ISSN: 2041-1723
Zusammenfassung: 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.
Enthalten in den Sammlungen:03 Fakultät Chemie

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Maier_et_al-2017-Nature_Communications.sup-1.pdfSupplementary information2,2 MBAdobe PDFÖffnen/Anzeigen


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