Boston University

The General Hospital Corporation

Minhee Park

Ahmad S Khalil

J Keith Joung

Jeffry D Sander

Divya Israni

Albert J Keung

Provided herein are engineered systems and methods for establishing DNA adenine methylation at specific genomic locations and using DNA adenine methylation as an artificial chemical 'handle' on the genome. These systems and methods allow for placing the handle on specific genomic locations as well as molecular technologies to bind, spatially spread, and maintain the handle. The systems described herein comprise, in some embodiments, three functional modules that mediate m6A operations: (1) a synthetic initiator module to place m6A at specific genomic sites; (2) a synthetic readout module to program m6A recognition and m6A-dependent transcriptional logic; and (3) propagation module that implements 'read-write,' a mechanism proposed to underlie chromatin spreading and epigenetic maintenance across cellular systems.

Integrated system for programmable DNA methylation

Embodiments disclosed herein provide artificial expression systems comprising the zinc-finger containing transcription factors and engineered promoters to modulate expression of genes of interest. Engineered zinc-finger transcription factors that interact with engineered promoters constitute synthetic and regulatable expression systems which facilitate the modulation of gene expression as desired.

Synthetic transcriptional and epigenetic regulators based on engineered, orthogonal zinc finger proteins

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Boston, MA, United States of America

Minhee Park