Comparative analysis reveals genomic features of stress-induced transcriptional readthrough

• DOI: 10.1073/pnas.1711120114
• Publication Date: 2017-09-20T00:40:16Z
• Authors: Anna Vilborg; Niv Sabath; Yuval Wiesel; Jenny Nathans; Flonia Levy-Adam; Therese A. Yario; Joan A. Steitz; Reut Shalgi
• Keywords: 0301 basic medicine; Genome; Transcription, Genetic; Gene Expression Profiling; Genomics; Mice; Oxidative Stress; 03 medical and health sciences; Gene Expression Regulation; Osmotic Pressure; NIH 3T3 Cells; Animals; Heat-Shock Response

Transcription is a highly regulated process, and stress-induced changes in gene transcription have been shown to play major role stress responses adaptation. Genome-wide studies reveal prevalent beyond known protein-coding loci, generating variety of RNA classes, most unknown function. One such class, termed downstream gene-containing transcripts (DoGs), was reported result from transcriptional readthrough upon osmotic human cells. However, how widespread the phenomenon is, what its causes consequences are, remain elusive. Here we present genome-wide mapping readthrough, using nuclear RNA-Seq, comparing heat shock, stress, oxidative NIH 3T3 mouse fibroblast We observe massive induction both levels length, under all conditions, with significant, yet not complete, overlap readthrough-induced loci between different conditions. Importantly, our analyses suggest that random failure but rather differentially induced across explore potential regulators find for HSF1 subset shock-induced transcripts. Analysis public datasets detected increases polymerase II occupancy DoG regions after supporting findings. Interestingly, DoGs tend be produced vicinity neighboring genes, leading marked increase their antisense-generating potential. Finally, examine genomic features unique chromatin signature typical DoG-producing regions, suggesting associated maintenance an open state.