We collaborated in a project where the CRISPR/dCas9 technology was adapted to work for epigenetic editing targeted to a precise genomic location and controlled by chemical induction [1]. This was obtained by adding the peptide motif FCPF to the C-terminal of Cas9, which can be recognized by perfluoro biphenyl (PFB). Then, addition of PFB conjugated to JQ1, a compound that inhibits BRD4, allows chemical induction of BRD4 inactivation at selected genomic positions. BRD4 is a protein that reads epigenetic marks to activate gene expression, and therefore its localized inhibition in the genome potentially reduces the activation of nearby genes. This was tested by specifically inhibiting BRD4 in the proximity to the promoters and enhancers of c-MYC using guide sgRNAs.
References
[1] Altinbay, M., J. Wang, J. Chen, D. Schäfer, M. Sprang, B. Blagojevic, S. Wölfl, M.A. Andrade-Navarro, I. Dikic, S. Knapp and X. Cheng. 2024. Chem-CRISPR/dCas9FCPF - a platform for chemically induced epigenome editing. Nucleic Acids Res. 52, 11587-11601. [>]