Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):E8362-E8371. doi: 10.1073/pnas.1711120114. Epub 2017 Sep 19.

Comparative analysis reveals genomic features of stress-induced transcriptional readthrough.

Author information

1
Department of Molecular Biophysics and Biochemistry, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536; vilborg.anna@gmail.com reutshalgi@technion.ac.il.
2
Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536.
3
Department of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel.
4
Department of Molecular Biophysics and Biochemistry, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06536.
5
Department of Biochemistry, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel vilborg.anna@gmail.com reutshalgi@technion.ac.il.

Abstract

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

KEYWORDS:

stress response; transcription regulation; transcriptional readthrough

PMID:
28928151
PMCID:
PMC5635911
DOI:
10.1073/pnas.1711120114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center