Research

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
Published April 8, 2014. Vol 24 Issue 6, pp. 896-905. https://doi.org/10.1101/gr.171405.113
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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.

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