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

Wing Fuk Chan; Hannah D. Coughlan; Yunshun Chen; Christine R. Keenan; Gordon K. Smyth; Andrew Charles Perkins; Timothy M. Johanson; Rhys S. Allan

doi:10.1038/s41467-022-33181-4

Synthetic BiologyNature CommunicationsSep 23, 2022

Peer-reviewed journal article

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

Wing Fuk Chan iD, Hannah D. Coughlan iD, Yunshun Chen iD, Christine R. Keenan iD, Gordon K. Smyth iD, Andrew Charles Perkins iD, Timothy M. Johanson iD, Rhys S. Allan iD

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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