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

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 syntheti

SUBMITTER: Maier JAH 

PROVIDER: S-EPMC5458116 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature