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. Author manuscript; available in PMC: 2018 Sep 1.
Published in final edited form as: Am J Med Genet B Neuropsychiatr Genet. 2017 Jul 12;174(6):631–640. doi: 10.1002/ajmg.b.32566

Figure 2.

Figure 2

(A) sgRNA small guide RNA directs Cas9 nuclease in sequence-specific manner to mediate DNA mutations (affected DNA shown in green). (B) nuclease-deficient Cas9 is fused to a de novo DNA methyltransferase, targeting a gene promoter region. Promoter methylation silences transcription. (C) In constrast, Cas9-bound VP64 (or the p300 catalytic subunit) functions as transcriptional activator via mechanisms that include recruitment of basal transcription factors (TF). (D). Higher order systems, including SunTag protein scaffold (see text) are able to further amplify transcriptional activity by even more than one magnitude (see text for further details).