an agent encoding a nuclease-null Cas9 protein that binds to DNA and is guided by one or more RNAs, which introduces into a cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA comprising a target nucleic acid 2 introducing the foreign nucleic acid into the cell, and introducing into the cell a third foreign nucleic acid encoding a transcriptional regulatory protein or domain, wherein at least one RNA, a nuclease-null Cas9 protein and a transcriptional regulatory protein or domain is expressed, wherein one or more RNA, a nuclease-null Cas9 protein and a transcriptional regulatory protein or domain are co-localized to DNA, wherein the transcriptional regulatory protein or domain regulates expression of the target nucleic acid; Methods are provided for modulating expression of a target nucleic acid in a cell.
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