TY - JOUR A1 - Wang, Zhong A1 - Chu, Tinyi A1 - Choate, Lauren A. A1 - Danko, Charles G. T1 - Identification of regulatory elements from nascent transcription using dREG Y1 - 2019/02/01 JF - Genome Research JO - Genome Research SP - 293 EP - 303 DO - 10.1101/gr.238279.118 VL - 29 IS - 2 UR - http://genome.cshlp.org/content/29/2/293.abstract N2 - Our genomes encode a wealth of transcription initiation regions (TIRs) that can be identified by their distinctive patterns of actively elongating RNA polymerase. We previously introduced dREG to identify TIRs using PRO-seq 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% improvement in accuracy, three- to fourfold 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-seq. Novel TIRs discovered by dREG were often associated with RNA polymerase III initiation, bound by pioneer transcription factors, or located in broad domains marked by repressive chromatin modifications. Our results suggest that transcription initiation can be a powerful tool for expanding the catalog of functional elements. ER -