Rate of elongation by RNA polymerase II is associated with specific gene features and epigenetic modifications.
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.
Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center and Translational Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA; Bioinformatics Program, Department of Computational Medicine and Bioinformatics and Department of Statistics, University of Michigan, Ann Arbor, Michigan 48109, USA;
Artur
A
Veloso
Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center and Translational Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA; Human Genetics Training Program, Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA;
Killeen S
KS
Kirkconnell
Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center and Translational Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA;
Brian
B
Magnuson
Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center and Translational Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA; Gustavus Adolphus College, St. Peter, Minnesota 56082, USA;
Benjamin
B
Biewen
Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center and Translational Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA;
Michelle T
MT
Paulsen
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA;
Thomas E
TE
Wilson
Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center and Translational Oncology Program, University of Michigan, Ann Arbor, Michigan 48109, USA; Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, USA.
Mats
M
Ljungman
D001482:Base Composition; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005091:Exons; D015894:Genome, Human; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D020079:Terminal Repeat Sequences; D061805:Transcription Elongation, Genetic
D006657:Histones; D012319:RNA Polymerase II