Determinants of Histone H3K4 Methylation Patterns
Open accessAbstract
Various factors differentially recognize trimethylated histone H3 lysine 4 (H3K4me3) near promoters, H3K4me2 just downstream, and promoter-distal H3K4me1 to modulate gene expression. This methylation "gradient" is thought to result from preferential binding of the H3K4 methyltransferase Set1/complex associated with Set1 (COMPASS) to promoter-proximal RNA polymerase II. However, other studies have suggested that location-specific cues allosterically activate Set1. Chromatin immunoprecipitation sequencing (ChIP-seq) experiments show that H3K4 methylation patterns on active genes are not universal or fixed and change in response to both transcription elongation rate and frequency as well as reduced COMPASS activity. Fusing Set1 to RNA polymerase II results in H3K4me2 throughout transcribed regions and similarly extended H3K4me3 on highly transcribed genes. Tethered Set1 still requires histone H2B ubiquitylation for activity. These results show that higher-level methylations reflect not only Set1/COMPASS recruitment but also multiple rounds of transcription. This model provides a simple explanation for non-canonical methylation patterns at some loci or in certain COMPASS mutants.
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Divergent H3K4me1 peaks were located further away from TSSs, flanking CGIs and H3K4me3 boundaries.
“Divergent H3K4me1 peaks were located further away from TSSs (Fig. 4a, b), which flanked CGIs and H3K4me3 boundaries44–46”
From Alternative promoters in CpG depleted regions are prevalently associated with epigenetic misregulation of liver cancer transcriptomes (2023) · cites this paper as [45]
The Results section (“H3K4 methylation patterns are not universal”; page unavailable) reports that H3K4me1 is generally shifted downstream relative to H3K4me2 and notes possible enrichment associated with divergent promoters. It does not report that divergent H3K4me1 peaks flank CGIs or H3K4me3 boundaries; that is the part most directly attached to this citation. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA 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 Soares et al, 2017
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References 58 · Cited by 209
- Authors
- Soares, L. M., He, P. C., Chun, Y., Suh, H., Kim, T., & Buratowski, S.
- Affiliations
- Harvard University (US)
- Corresponding author
- Buratowski, Stephen
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 68
- Issue
- 4
- Pages
- 773-785.e6
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5706784
- OpenAlex
- W2767770944
- Cited by
- 209
- References
- 58
- Citations by year
- 2026: 20 · 2025: 18 · 2024: 22 · 2023: 19 · 2022: 31 · 2021: 39 · 2020: 26 · 2019: 21 · 2018: 13
- FWCI
- 6.70
- 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 (GM46498, GM56663)
- Korean National Research Foundation (2013S1A2A2035342)
- Harvard College Research Program
- 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 › Chromatin Remodeling and Cancer
- Keywords
- histone H3 lysine 4 methylation, H3K4me3, H3K4me2, H3K4me1, COMPASS complex, Set1, RNA polymerase II, transcription elongation, histone H2B ubiquitylation, allosteric activation, gene expression regulation
- MeSH terms
- Histones, Methylation, Models, Biological, Histone-Lysine N-Methyltransferase, Saccharomyces cerevisiae, Schizosaccharomyces, Transcription Factors, Schizosaccharomyces pombe Proteins, Ubiquitination
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