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Nature CommunicationsSynthetic BiologyPeer-reviewed journal article

Activation of stably silenced genes by recruitment of a synthetic de-methylating module

Wing Fuk ChaniD, Hannah D. CoughlaniD, Yunshun CheniD, Christine R. KeenaniD, Gordon K. SmythiD, Andrew Charles PerkinsiD, Timothy M. JohansoniD, Rhys S. AllaniD

PDFDOIPreprint

Abstract

Stably silenced genes that display a high level of CpG dinucleotide methylation are refractory to the current generation of dCas9-based activation systems. To counter this, we created an improved activation system by coupling the catalytic domain of DNA demethylating enzyme TET1 with transcriptional activators (TETact). TETact induces transcription of heavily suppressed non-coding RNA and surface protein, and the reactivation of embryonic haemoglobin genes in non-erythroid cells.

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