This protocol describes the steps needed to design and perform multiplexed targeting of enhancers with the deactivating fusion protein SID4X-dCas9-KRAB, also known as enhancer interference (Enhancer-i). This protocol enables the identification of enhancers that regulate gene expression and facilitates the dissection of relationships between enhancers regulating a common target gene.
Carleton, J. B., Berrett, K. C., Gertz, J. Dissection of Enhancer Function Using Multiplex CRISPR-based Enhancer Interference in Cell Lines. J. Vis. Exp. (136), e57883, doi:10.3791/57883 (2018).