RNA Pol II Dynamics Modulate Co-transcriptional Chromatin Modification, CTD Phosphorylation, and Transcriptional Direction
Open accessAbstract
Eukaryotic genes are marked by conserved post-translational modifications on the RNA pol II C-terminal domain (CTD) and the chromatin template. How the 5'-3' profiles of these marks are established is poorly understood. Using pol II mutants in human cells, we found that slow transcription repositioned specific co-transcriptionally deposited chromatin modifications; histone H3 lysine 36 trimethyl (H3K36me3) shifted within genes toward 5' ends, and histone H3 lysine 4 dimethyl (H3K4me2) extended farther upstream of start sites. Slow transcription also evoked a hyperphosphorylation of CTD Ser2 residues at 5' ends of genes that is conserved in yeast. We propose a "dwell time in the target zone" model to explain the effects of transcriptional dynamics on the establishment of co-transcriptionally deposited protein modifications. Promoter-proximal Ser2 phosphorylation is associated with a longer pol II dwell time at start sites and reduced transcriptional polarity because of strongly enhanced divergent antisense transcription at promoters. These results demonstrate that pol II dynamics help govern the decision between sense and divergent antisense transcription.
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A fast RNA Pol II mutant shifts H3K4me2/me3 in the 3′ direction, while a slow mutant shifts these marks toward the 5′ end of genes.
“Moreover, a fast RNA Pol II mutant shifts H3K4me2/me3 in the 3′ direction (Soares et al, 2017), while a slow RNA Pol II mutant shifts these marks toward the 5′ end of genes (Fong et al, 2017; Soares et al, 2017).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Fong et al, 2017
The Results section (page not supplied) reports that the slow R749H mutant increases H3K4me2 upstream of transcription start sites and reduces it immediately downstream. It also says H3K4me3 is relatively insensitive to Pol II dynamics, so Fong et al. support the slow-mutant claim for H3K4me2, but not H3K4me3. The fast-mutant clause is attributed to Soares et al., not Fong et al. (LLM, conf=0.90)
Experimental — accuracy not yet measuredThe dwell time spent by RNA Pol II within the target zone where it associates with a modifier can modulate the deposition or removal of post-translational modifications.
“These results suggest that the dwell time spent by RNA Pol II within the “target zone” where it associates with a modifier can modulate the deposition or removal of post‐translational modifications (Fong et al, 2017).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Fong et al, 2017
Slow RNA Pol II mutants shift RNA Pol II Ser2 hyperphosphorylation to the 5′ end of genes.
“Moreover, slow RNA Pol II mutants shift RNA Pol II Ser2 hyperphosphorylation to the 5′ end of genes (Fong et al, 2017).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Fong et al, 2017
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References 63 · Cited by 98
- Authors
- Fong, N., Saldi, T., Sheridan, R. M., Cortazar, M. A., & Bentley, D. L.
- Affiliations
- University of Colorado Anschutz (US)
- Corresponding author
- Bentley, David L.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 66
- Issue
- 4
- Pages
- 546-557.e3
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5488731
- OpenAlex
- W2612265006
- Cited by
- 98
- References
- 63
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 8 · 2023: 11 · 2022: 12 · 2021: 6 · 2020: 18 · 2019: 18 · 2018: 12 · 2017: 4
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (GM58613, R35GM118051)
- American Cancer Society (PF-15-188-01-RMC)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- RNA polymerase II, C-terminal domain phosphorylation, H3K36me3, H3K4me2, transcriptional dynamics, histone modifications
- MeSH terms
- Protein Domains, Chromatin, DNA, Fungal, Humans, Mutation, Phosphorylation, RNA Polymerase II, Saccharomyces cerevisiae, Time Factors, Transcription, Genetic, Gene Expression Regulation, Fungal, Saccharomyces cerevisiae Proteins, Chromatin Assembly and Disassembly, HEK293 Cells
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