Inner-cell compounds steer CRISPR to activate genes
CRISPR can be used not only to edit genes, but also to influence their expression. Technology, sometimes called CRISPRi (i stands for interference), uses dCas9, which finds a specific sequence and binds itself to it – but unlike standard Cas9, dCas9 does not cut the DNA, staying attached to the genome. In that way, it can influence gene expression by attracting or blocking proteins involved in expression.
Scientists from US’ collaboration expanded dCas9 by attaching to it FK506-binding protein (FKBP). Thanks to that, new CRISPR-associated protein can be binded CEMs: chemical epigenetic modifiers. It was tested with three CEMs: CEM87 (BRD4), CEM88 (BRPF1), and CEM114 (CBP/p300). In result, genes targeted by CRISPR were upregulated over 20-fold in a dose-dependent manner.
Study presents the next step on the way to more controllable and specific CRISPR toolbox.
Publication: Chiarella, A.M., Butler, K.V., Gryder, B.E. et al. Dose-dependent activation of gene expression is achieved using CRISPR and small molecules that recruit endogenous chromatin machinery. Nat Biotechnol (2019) doi:10.1038/s41587-019-0296-7