Rate of elongation by RNA polymerase II is associated with specific gene features and epigenetic modifications
Open accessAbstract
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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H3K79me2, H2B mono-ubiquitylation, and H4K20me1 positively correlate with RNA Pol II speed in the gene body.
“Genome‐wide studies have shown that H3K79me2, H2B mono‐ubiquitylation, and H4K20me1 positively correlate with RNA Pol II speed in the gene body (Fuchs et al, 2014a; Jonkers et al, 2014; Veloso et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Veloso et al, 2014
The Results section (Figure 4 and “Elongation rates are related to specific epigenetic modifications”; page unavailable) reports that H3K79me2 and H4K20me1 positively correlate with elongation rates, including higher modification density within gene bodies of faster-elongating genes. The cited paper does not report the claimed correlation for H2B mono-ubiquitylation. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTranscription speed on individual genes is overall well conserved between cell lines.
“In addition, comparison of transcription speed between different cell lines showed that transcription speed on individual genes is overall well conserved between cell lines (Singh & Padgett, 2009; Veloso et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Veloso et al, 2014
GC content within gene bodies correlates negatively with RNA Pol II speed.
“Moreover, the GC content within gene bodies has been shown to correlate negatively with RNA Pol II speed (Jonkers et al, 2014; Veloso et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Veloso et al, 2014
Exon density correlates negatively with RNA Pol II velocity.
“Conversely, exon density correlates negatively with RNA Pol II velocity (Jonkers et al, 2014; Veloso et al, 2014)”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Veloso et al, 2014
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“Conversely, exon density correlates negatively with RNA Pol II velocity (Jonkers et al , 2014; Veloso et al , 2014), which may be the result of several contributing factors.”
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- Authors
- Veloso, A., Kirkconnell, K. S., Magnuson, B., Biewen, B., Paulsen, M. T., Wilson, T. E., & Ljungman, M.
- Affiliations
- University of Michigan (US)
- Gustavus Adolphus College (US)
- Corresponding author
- Ljungman, Mats
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2014-04-08
- Volume
- 24
- Issue
- 6
- Pages
- 896-905
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC4032854
- OpenAlex
- W2099793004
- Cited by
- 281
- References
- 50
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 26 · 2023: 24 · 2022: 27 · 2021: 35 · 2020: 17 · 2019: 41 · 2018: 20 · 2017: 20 · 2016: 21 · 2015: 16 · 2014: 8
- Type
- posted content
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Genome Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- University of Michigan (P50CA130810)
- National Institutes of Health (5r21es020946-02)
- National Human Genome Research Institute (R01HG006786)
- National Cancer Institute (P50CA130810)
- National Institute of General Medical Sciences (T32GM007544)
- National Institute of Environmental Health Sciences (R21-ES020946, 1R21ES020946, P30ES017885)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- RNA polymerase II, DRB, H3K79me2, H4K20me1, histone modifications, DNA methylation, gene length, GC content, long terminal repeat, alternative splicing, epigenetic regulation, human cells
- MeSH terms
- Base Composition, Exons, Histones, Humans, RNA Polymerase II, Genome, Human, DNA Methylation, Terminal Repeat Sequences, Epigenesis, Genetic, Transcription Elongation, Genetic, MCF-7 Cells
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