报告题目：High-Resolution Mapping of RNA Polymerases Identifies Enhancers & microRNA TSS
报 告 人: Dr. Jing Wang Research fellow
Center for Quantitative Sciences, Vanderbilt University Medical Center
Global nuclear run-on sequencing (GRO-seq) and precision nuclear run-on transcription sequencing (PRO-seq), creating high-resolution maps of active RNA polymerases, provide powerful techniques to study the entire nascent transcriptome, especially enhancer RNAs. We present a tool, Nascent RNA Sequencing Analysis (NRSA), for transcriptional analysis of active genes and enhancers in GRO/PRO-seq data. In addition to enhancer detection, annotation and quantification, NRSA prioritizes functional important enhancers by integrating co-transcriptional changes between enhancers and their target genes and the corresponding ChIP-seq data. NRSA achieved better performance for enhancer identification than existing GRO/PRO-seq- or histone-marker-based methods. Applied to wildtype and histone deacetylase 3 (Hdac3) knockout PRO-seq data, NRSA identified functional important enhancers, which mediate the regulation of Hdac3. In addition, we develop mirSTP (mirna transcription Start sites Tracking Program) to identify active miRNA TSSs using characteristic bidirectional transcription signatures at promoters in GRO/PRO-seq data. mirSTP demonstrated better performance than existing methods. mirSTP analysis of 27 human cell lines in 183 GRO-seq and 28 PRO-seq experiments identified TSSs for 480 intergenic miRNAs. Integrating with matched ENCODE transcription factor ChIP-seq data, we provides a valuable source for understanding the complex interplay between transcription factor and miRNA. These tools/methods will greatly facilitate the usage of GRO/PRO-seq techniques and benefit research on transcriptional regulation.