title: Quantitatively predictable control of Drosophila transcriptional enhancers in vivo with engineered transcription factors.
abstract: Genes are regulated by transcription factors that bind to regions of genomic DNA called enhancers. Considerable effort is focused on identifying transcription factor binding sites, with the goal of predicting gene expression from DNA sequence. Despite this effort, general, predictive models of enhancer function are currently lacking. Here we combine quantitative models of enhancer function with manipulations using engineered transcription factors to examine the extent to which enhancer function can be controlled in a quantitatively predictable manner. Our models, which incorporate few free parameters, can accurately predict the contributions of ectopic transcription factor inputs. These models allow the predictable 'tuning' of enhancers, providing a framework for the quantitative control of enhancers with engineered transcription factors.
authors: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.
authors: Justin
authors: J
authors: Crocker
authors: Okinawa Institute of Science and Technology Graduate University, Onna, Japan.
authors: Garth R
authors: http://orcid.org/0000-0001-9863-5802
authors: GR
authors: Ilsley
authors: Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA.
authors: David L
authors: DL
authors: Stern
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D008957:Models, Genetic; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors