@article{42f4b47b2fc34d8b80cc57ae2dd5265f,
title = "Activation of stably silenced genes by recruitment of a synthetic de-methylating module",
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 create an improved activation system by coupling the catalytic domain of DNA demethylating enzyme TET1 with transcriptional activators (TETact). We show that TETact demethylation-coupled activation is able to induce transcription of suppressed genes, both individually and simultaneously in cells, and has utility across a number of cell types. Furthermore, we show that TETact can effectively reactivate embryonic haemoglobin genes in non-erythroid cells. We anticipate that TETact will expand the existing CRISPR toolbox and be valuable for functional studies, genetic screens and potential therapeutics.",
author = "Chan, {Wing Fuk} and Coughlan, {Hannah D.} and Yunshun Chen and Keenan, {Christine R.} and Smyth, {Gordon K.} and Perkins, {Andrew C.} and Johanson, {Timothy M.} and Allan, {Rhys S.}",
note = "Funding Information: We thank the staff of the core facilities at the Walter and Eliza Hall Institute. This work was supported by grants and fellowships from the Marian and E.H. Flack Fellowship (H.D.C.), the National Health and Medical Research Council of Australia (C.R.K #1125436, T.M.J. #1124081, R.S.A. #1100451, G.K.S. & R.S.A. #1158531), Medical Research Future Fund (MRFF) Investigator Grant (Y.C. #1176199) and the Australian Research Council (R.S.A. #130100541). This study was made possible through Victorian State Government Operational Infrastructure Support, the Australian Government NHMRC Independent Research Institute Infrastructure Support scheme, and the Australian Cancer Research Fund. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-33181-4",
language = "English",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}