H3K9 methylation and RNA interference regulate nucleolar organization and repeated DNA stability
Open accessAbstract
Investigations aimed at identifying regulators of nuclear architecture in Drosophila demonstrated that cells lacking H3K9 methylation and RNA interference (RNAi) pathway components displayed disorganized nucleoli, ribosomal DNA (rDNA) and satellite DNAs. The levels of H3K9 dimethylation (H3K9me2) in chromatin associated with repeated DNAs decreased dramatically in Su(var)3-9 and dcr-2 (dicer-2) mutant tissues compared with wild type. We also observed a substantial increase in extrachromosomal circular (ecc) repeated DNAs in mutant tissues. The disorganized nucleolus phenotype depends on the presence of Ligase 4 and ecc DNA formation is not induced by removal of cohesin. We conclude that the structural integrity and organization of repeated DNAs and nucleoli are regulated by the H3K9 methylation and RNAi pathways, and other regulators of heterochromatin-mediated silencing. In addition, repeated DNA stability involves suppression of non-homologous end joining (NHEJ) or other recombination pathways. These results suggest a mechanism for how local chromatin structure can regulate genome stability, and the organization of chromosomal elements and nuclear organelles.
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Maintaining a subset of rRNA genes in an inactive heterochromatic state is thought to be important for ensuring nucleolar structure and preventing recombination between rDNA repeats.
“Second, maintaining a subset of rRNA genes in an inactive heterochromatic state is thought to be important for ensuring nucleolar structure and preventing recombination between rDNA repeats (22–24).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [22]
In D. melanogaster, heterochromatin components are implicated in maintaining the nucleolar structure and preventing recombination between rDNA repeats, as well as in nucleolar dominance.
“In D. melanogaster, heterochromatin components have been shown to be implicated in maintaining the nucleolar structure and preventing recombination between rDNA repeats (22), as well as in nucleolar dominance, a phenomenon whereby an entire rDNA cluster is silenced (104).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [22]
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Heterochromatin: Guardian of the Genome
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Self-citation<i>Drosophila</i> PIWI associates with chromatin and interacts directly with HP1a
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Heterochromatic Genome Stability Requires Regulators of Histone H3 K9 Methylation
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“nents have been shown to be implicated in maintaining the nucleolar structure and preventing recombination between rDNA repeats (22), as well as in nucleolar dominance, a phenomenon whereby an entire rDNA cluster is silenced (104).”
Background
- Authors
- Peng, J. C., & Karpen, G. H.
- Affiliations
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Karpen, Gary H.
- Venue
- Nature Cell Biology
- Published
- 2006-12-10
- Volume
- 9
- Issue
- 1
- Pages
- 25-35
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC2819265
- OpenAlex
- W2011068062
- Cited by
- 375
- References
- 3
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 9 · 2023: 12 · 2022: 17 · 2021: 16 · 2020: 27 · 2019: 18 · 2018: 15 · 2017: 30 · 2016: 20 · 2015: 28 · 2014: 30 · 2013: 19 · 2012: 22
- FWCI
- 9.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM066272, R01GM061169)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- H3K9 methylation, RNA interference, nucleolar organization, ribosomal DNA, satellite DNA, extrachromosomal circular DNA, Su(var)3-9, Dicer-2, cohesin, heterochromatin, genome stability, nuclear organization, non-homologous end joining, Drosophila
- MeSH terms
- Cohesins, Animals, Cell Nucleolus, Chromosomal Proteins, Non-Histone, DNA, Ribosomal, DNA, Satellite, Drosophila, Heterochromatin, Histones, Models, Genetic, Nuclear Proteins, Repressor Proteins, Cell Cycle Proteins, DNA Methylation, Drosophila Proteins, RNA Interference, Protein Inhibitors of Activated STAT
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