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generate synthetic CRISPR-based transcriptional largely by the pattern of transcriptional activators, repressors, or other regulators that assemble at distinct sites in the genome.complex transcriptional programs that allow a single genome to be interpreted in numerous, distinct ways. In these programs, specific loci throughout the genome must be regulated indepen-(dCas9) protein, which lacks endonuclease activity, can be used to flexibly target many loci in parallel by using Cas9-binding guide RNAs that recognize target DNA sequences based only ondently. For example, during development, it is often critical to activate sets of genes associated with a new cell fate while predictable Watson-Crick base pairing. CRISPRi regulation can be used to achieve activation or repression by fusing dCas9 toprograms in yeast and human cells. By extending guide RNAs to include effector protein recruitment sites, we construct modular scaffold RNAs that encode both target locus and regulatory action. Sets of scaffold RNAs can be used to generate synthetic multigene transcriptional programs in which some genes are activated and others are repressed. We apply this approach to flexibly redirect flux through a complex branched metabolic pathway in yeast. Moreover, these programs can be executed by inducing expression of the dCas9 protein, which acts as a single master regulatory control point. CRISPR-associated RNA scaffolds provide a power-ful way to construct synthetic gene expression pro-grams for a wide range of applications, including rewiring cell fatesor engineeringmetabolicpathways