Degenerate Pax2 and Senseless binding motifs improve detection of low-affinity sites required for enhancer specificity.

ABSTRACT: Cells use thousands of regulatory sequences to recruit transcription factors (TFs) and produce specific transcriptional outcomes. Since TFs bind degenerate DNA sequences, discriminating functional TF binding sites (TFBSs) from background sequences represents a significant challenge. Here, we show that a Drosophila regulatory element that activates Epidermal Growth Factor signaling requires overlapping, low-affinity TFBSs for competing TFs (Pax2 and Senseless) to ensure cell- and segment-specific activity. Testing available TF binding models for Pax2 and Senseless, however, revealed variable accuracy in predicting such low-affinity TFBSs. To better define parameters that increase accuracy, we developed a method that systematically selects subsets of TFBSs based on predicted affinity to gene

SUBMITTER: Zandvakili A 

PROVIDER: S-EPMC5902045 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature