Rate of elongation by RNA polymerase II is associated with specific gene features and epigenetic modifications

Artur Veloso; Killeen S. Kirkconnell; Brian Magnuson; Benjamin Biewen; Michelle T. Paulsen; Thomas E. Wilson; Mats Ljungman

doi:10.1101/gr.171405.113

Rate of elongation by RNA polymerase II is associated with specific gene features and epigenetic modifications

¹Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center and Translational Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA;
²Bioinformatics Program, Department of Computational Medicine and Bioinformatics and Department of Statistics, University of Michigan, Ann Arbor, Michigan 48109, USA;
³Human Genetics Training Program, Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA;
⁴Gustavus Adolphus College, St. Peter, Minnesota 56082, USA;
⁵Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA;
⁶Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA;
⁷Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA

Abstract

The rate of transcription elongation plays an important role in the timing of expression of full-length transcripts as well as in the regulation of alternative splicing. In this study, we coupled Bru-seq technology with 5,6-dichlorobenzimidazole 1-β-D-ribofuranoside (DRB) to estimate the elongation rates of over 2000 individual genes in human cells. This technique, BruDRB-seq, revealed gene-specific differences in elongation rates with a median rate of around 1.5 kb/min. We found that genes with rapid elongation rates showed higher densities of H3K79me2 and H4K20me1 histone marks compared to slower elongating genes. Furthermore, high elongation rates had a positive correlation with gene length, low complexity DNA sequence, and distance from the nearest active transcription unit. Features that negatively correlated with elongation rate included the density of exons, long terminal repeats, GC content of the gene, and DNA methylation density in the bodies of genes. Our results suggest that some static gene features influence transcription elongation rates and that cells may alter elongation rates by epigenetic regulation. The BruDRB-seq technique offers new opportunities to interrogate mechanisms of regulation of transcription elongation.

Footnotes

↵8 Corresponding author

E-mail Ljungman{at}umich.edu
[Supplemental material is available for this article.]
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.171405.113.

Received December 17, 2013.
Accepted April 1, 2014.

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