Activation of stably silenced genes by recruitment of a synthetic de-methylating module.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36151095.
- Also identified by DOI 10.1038/s41467-022-33181-4 and PMC identifier 9508233.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- CRISPR-Cas Systems
- DNA Methylation