TALE-mediated modulation of transcriptional enhancers

We tested whether Transcription Activator-Like Effectors (TALEs) can mediate repression and activation of endogenous enhancers in the Drosophila genome. TALE-repressors (TALERs) targeting each of the five even-skipped (eve) “stripe” enhancers generated repression specifically of the focal stripes. TALE-activators (TALEAs) targeting the eve promoter or eve enhancers caused increased expression primarily in cells normally activated by the promoter or targeted enhancer, respectfully. The phenotypic effects of TALER and TALEA expression in larvae and adults are consistent with the observed modulations of eve expression. In these assays, the Hairy repression domain did not exhibit previously described long-range transcriptional repression activity. The precise effects of the TALEAs support the view that repression acts in a dominant fashion on transcriptional activators and that the activity state of an enhancer influences TALE binding or the ability of VP16 to enhance transcription. TALEs thus provide a novel tool for detection and functional modulation of transcriptional enhancers in their native genomic context.