Tracking Transcription Factors on the Genome by their DNase-seq Footprints

Abstract

AbstractTranscription factors control numerous vital processes in the cell through their ability to control gene expression. Dysfunctional regulation by transcription factors lead to disorders and disease. Transcription factors regulate gene expression by binding to DNA sequences (motifs) on the genome and altering chromatin. DNase-seq footprinting is a well-established assay for identification of DNA sequences that bind to transcription factors. We developed computational techniques to analyze footprints and predict transcription factor binding. These transcription factor specific predictive models are able to correct for DNase sequence bias and characterize variation in DNA binding sequence. We found that DNase-seq footprints are able to identify cell-type or condition specific transcription factor activity and may offer information about the type of the interaction between DNA and transcription factor. Our DNase-seq footprint model is able to accurately discover high confidence transcription factor binding sites and discover alternative interactions between transcription factors and DNA. DNase-seq footprints can be used with ChIP-seq data to discover true binding sites and better understand transcription regulation.