Abstract
Our genomes encode a wealth of transcription initiation regions (TIRs) that can be identified by their distinctive patterns of transcription initiation. We previously introduced dREG to identify TIRs using PROseq data. Here we introduce an efficient new implementation of dREG that uses PRO-seq data to identify both uni- and bidirectionally transcribed TIRs with 70% improvements in accuracy, 3–4-fold higher resolution, and >100-fold increases in computational efficiency. Using a novel strategy to identify TIRs based on their statistical confidence reveals extensive overlap with orthogonal assays, yet also reveals thousands of additional weakly-transcribed TIRs that were not identified by H3K27ac ChIP-seq or DNase-I-hypersensitivity. Novel TIRs discovered by dREG were often associated with RNA polymerase III initiation or bound by transcription factors that recognize DNA concurrently with a nucleosome. We provide a web interface to dREG that can be used by the scientific community (http://dREG.DNASequence.org).
