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Step-Wise Methylation of Histone H3K9 Positions Heterochromatin at the Nuclear Periphery
Open accessAbstract
The factors that sequester transcriptionally repressed heterochromatin at the nuclear periphery are currently unknown. In a genome-wide RNAi screen, we found that depletion of S-adenosylmethionine (SAM) synthetase reduces histone methylation globally and causes derepression and release of heterochromatin from the nuclear periphery in Caenorhabditis elegans embryos. Analysis of histone methyltransferases (HMTs) showed that elimination of two HMTs, MET-2 and SET-25, mimics the loss of SAM synthetase, abrogating the perinuclear attachment of heterochromatic transgenes and of native chromosomal arms rich in histone H3 lysine 9 methylation. The two HMTs target H3K9 in a consecutive fashion: MET-2, a SETDB1 homolog, mediates mono- and dimethylation, and SET-25, a previously uncharacterized HMT, deposits H3K9me3. SET-25 colocalizes with its own product in perinuclear foci, in a manner dependent on H3K9me3, but not on its catalytic domain. This colocalization suggests an autonomous, self-reinforcing mechanism for the establishment and propagation of repeat-rich heterochromatin.
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“A number of recent reports demonstrate that histone and DNA methylation is sensitive to alterations in SAM levels (Chiang et al., 2009; Shyh-Chang et al., 2013; Towbin et al., 2012).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Towbin et al., 2012
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Metadata
- Authors
- Towbin, B. D., González-Aguilera, C., Sack, R., Gaidatzis, D., Kalck, V., Meister, P., Askjaer, P., & Gasser, S. M.
- Affiliations
- University of Basel (CH)
- Friedrich Miescher Institute (CH)
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Gasser, Susan M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-08
- Volume
- 150
- Issue
- 5
- Pages
- 934-947
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2033160626
- Cited by
- 597
- References
- 54
- Citations by year
- 2026: 29 · 2025: 33 · 2024: 39 · 2023: 24 · 2022: 36 · 2021: 42 · 2020: 51 · 2019: 42 · 2018: 57 · 2017: 45 · 2016: 56 · 2015: 48 · 2014: 42 · 2013: 45 · 2012: 7
- FWCI
- 18.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- BORIS (University Library Bern) (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, other-oa)
- 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 › Nuclear Structure and Function
- Keywords
- heterochromatin, nuclear periphery, histone H3 lysine 9 methylation, histone methyltransferase, MET-2, S-adenosylmethionine synthetase, H3K9me3, chromatin condensation, Caenorhabditis elegans embryo, RNAi screen
- MeSH terms
- Animals, Cell Nucleus, Chromosomes, Embryo, Nonmammalian, Heterochromatin, Histones, Methionine Adenosyltransferase, Methylation, Mutation, Histone-Lysine N-Methyltransferase, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Lamins, Genome, Helminth
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