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In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse
Open accessAbstract
Methylation of cytosines (5meC) is a widespread heritable DNA modification. During mammalian development, two global demethylation events are followed by waves of de novo DNA methylation. In vivo mechanisms of DNA methylation establishment are largely uncharacterized. Here, we use Saccharomyces cerevisiae as a system lacking DNA methylation to define the chromatin features influencing the activity of the murine DNMT3B. Our data demonstrate that DNMT3B and H3K4 methylation are mutually exclusive and that DNMT3B is co-localized with H3K36 methylated regions. In support of this observation, DNA methylation analysis in yeast strains without Set1 and Set2 shows an increase of relative 5meC levels at the transcription start site and a decrease in the gene-body, respectively. We extend our observation to the murine male germline, where H3K4me3 is strongly anti-correlated while H3K36me3 correlates with accelerated DNA methylation. These results show the importance of H3K36 methylation for gene-body DNA methylation in vivo.
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“studies have suggested that the patterns of DNA methyltransferase localization, DNA methylation, and actively transcribed gene bodies may be specified by histone modifications.113,114”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [114]
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“Studies with mESC and a heterologous yeast system found that the establishment of intragenic 5mC is a controlled process carried out by de novo DNA methyltransferase DNMT3B and co-transcriptionally regulated histone modification H3K36me (32, 33).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [33]
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Metadata
- Authors
- Morselli, M., Pastor, W. A., Montanini, B., Nee, K., Ferrari, R., Fu, K., Bonora, G., Rubbi, L., Clark, A. T., Ottonello, S., Jacobsen, S. E., & Pellegrini, M.
- Affiliations
- University of California, Los Angeles (US)
- University of Parma (IT)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Morselli, Marco
- Jacobsen, Steven E
- Pellegrini, Matteo
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2015-04-07
- Volume
- 4
- Pages
- e06205-e06205
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC4412109
- OpenAlex
- W2087785865
- Cited by
- 167
- References
- 59
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 11 · 2023: 17 · 2022: 10 · 2021: 16 · 2020: 19 · 2019: 22 · 2018: 16 · 2017: 17 · 2016: 13 · 2015: 10
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Update notices
- correction (2017-08-31)
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (NIH) (R01 GM095656-01A1, GM60398)
- National Institute of Child Health and Human Development (NICHD) (R01HD058047)
- Howard Hughes Medical Institute (HHMI)
- Jane Coffin Childs Memorial Fund for Medical Research
- Whitcome Fellowship
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- de novo methylation, histone modifications, DNMT3B, H3K4 methylation, H3K36 methylation, Saccharomyces cerevisiae, Set1, Set2, gene body methylation, transcription start sites, male germline, chromatin
- MeSH terms
- DNA Methyltransferase 3B, Animals, Chromatin, Cytosine, DNA (Cytosine-5-)-Methyltransferases, Embryo, Mammalian, Genetic Vectors, Germ Cells, Histones, Male, Methyltransferases, Histone-Lysine N-Methyltransferase, Saccharomyces cerevisiae, Transformation, Genetic, Signal Transduction, Open Reading Frames, Gene Expression Regulation, Developmental, CpG Islands, DNA Methylation, Protein Isoforms, Transcription Initiation Site, Saccharomyces cerevisiae Proteins, Mice
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