(a) Schematics of SAM. SAM consists of two chimeric proteins, dCas9 fused with VP64 and MS2-coat protein fused with p65 and HSF1 activator domains (MS2-NLS-p65-HSF1), and an sgRNA having MS2 aptamers in stem loops, known as sgRNA 2.0. MS2 aptamers in sgRNA recruits MS2-NLS-p65-HSF1, so this system can simultaneously recruit VP64, p65 and HSF1. (b) Schematics of dCas9-Suntag. dCas9-Suntag consists of two chimeric proteins, dCas9 fused with 10 copies of a GCN4 peptide and single-chain variable fragment nanobody (scFv) for GCN4 fused with VP64 activator domains (scFv-VP64), and an sgRNA. Because scFv-VP64 strongly binds to GCN4 peptides, this system can recruit multiple VP64 into Cas9-targeted locus. (c) Schematics of dCas9-VPR. VPR is a potent tripartite activator consisting of VP64, p65AD and the Epstein-Barr virus R transactivator Rta.