Reading of Epigenetic Information and Design of Epigenetic Memory Systems

I will present our progress in three projects related to reading and writing of epigenetic information. The first deals with the triple Tudor domain (3TD) of SETDB1, which we have recently shown to be reader for combined methylation at K9 and acetylation at K14. Our structural and biochemical data show that different methylation states at K9 are recognized by different pockets of the 3TD and that the 3TD domain has an important role in the targeting of SETDB1 in cells. Afterwards, I will present our recent results regarding the locus specific detection epigenetic modifications in live cells. The system is based on fluorescence complementation between a designed DNA binding domain for genomic targeting und a reading domains for chromatin modifications. Finally, I will describe our recent results in designing artificial epigenetic networks in bacteria which are based on DNA methylation and artificial designed Zinc finger proteins. The systems feature positive feedback, reversible switching and memory effects and could be used for bacterial biosensors.

References:

Jurkowska et al. H3K14ac is linked to methylation of H3K9 by the triple Tudor domain of SETDB1. Nat. Commun., in press.

Lungu C, Pinter S, Broche J, Rathert P, Jeltsch A. Modular fluorescence complementation sensors for live cell detection of epigenetic signals at endogenous genomic sites. Nat Commun. 2017 Sep 21;8(1):649.

Maier JAH, Möhrle R, Jeltsch A. Design of synthetic epigenetic circuits featuring memory effects and reversible switching based on DNA methylation. Nat Commun. 2017 May 24;8:15336.