Cited by 606Genomics and Chromatin DynamicsEpigenetics and DNA MethylationNuclear Structure and Function

Step-wise methylation of histone H3K9 positions heterochromatin at the nuclear periphery

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Towbin, Benjamin D., González-Aguilera, Cristina, Sack, Ragna, Gaidatzis, Dimos, Kalck, Véronique, Meister, Peter, Askjaer, Peter, Gasser, Susan M.·2012·Cell

Abstract

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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Crossref · 10.1016/j.cell.2012.06.051

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  • Histone and DNA methylation is sensitive to alterations in SAM levels.

    “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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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
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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