RNA Innovation Seminar: Haiyuan Yu, Cornell University

“Dissect Enhancer Architecture and Map Regulatory Genomic Landscape Across Diverse Cell and Tissue Types Through Nascent Transcriptome Studies”
Haiyuan Yu, Ph.D.
Tisch University Professor
Department of Biological Statistics and Computational Biology
Weill Institute for Cell and Molecular Biology
Director, Center for Innovative Proteomics (CIP@Cornell)

In-person: BSRB, ABC seminar rooms / hybrid link

Abstract: Recent studies have shown that both enhancers and promoters can recruit RNA pol II and initiate transcription. The short half-life nature of enhancer RNAs (eRNAs) makes detection of distal initiation events challenging. Through systematic comparison of RNA sequencing assays, we find that nascent transcriptome assays, PRO-cap and PRO-seq, have great sensitivity and specificity in detecting eRNA transcription genome-wide. In fact, we find that, unlike histone marks, divergent transcription of eRNAs is a critical mark for all active enhancers genome-wide. Moreover, nascent transcription precisely delineates the sequence architecture of enhancers, whereby transcription start sites (TSSs) serve as critical anchors in revealing motif positioning within enhancers and their boundaries. By leveraging our high precision and sensitivity nascent transcriptome PRO-cap and PRO-seq assays, we mapped the active transcriptional regulatory landscape across ~200 tissue and cell types of the human body with unprecedented resolution and depth. This information is used to quantify gene transcriptional activity and to identify and delineate transcription regulatory elements, including both enhancers and promoters that are cell-type-specific and ubiquitous. These findings are critical in modeling putative enhancer-promoter connectivity and in speeding the identification of potential disease-associated noncoding variants in regulatory regions.