The nucleolar remodeling complex NoRC mediates heterochromatin formation and silencing of ribosomal gene transcription
Abstract
Epigenetic control mechanisms silence about half of the ribosomal RNA (rRNA) genes in metabolically active cells. In exploring the mechanism by which the active or silent state of rRNA genes is inherited, we found that NoRC, a nucleolar remodeling complex containing Snf2h (also called Smarca5, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin, subfamily a, member 5), represses rDNA transcription. NoRC mediates rDNA silencing by recruiting DNA methyltransferase and histone deacetylase activity to the rDNA promoter, thus establishing structural characteristics of heterochromatin such as DNA methylation, histone hypoacetylation and methylation of the Lys9 residue of histone H3. These results indicate that active and inactive rRNA genes can be demarcated by their associated proteins, and link chromatin remodeling to DNA methylation and specific histone modifications.
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Silent rRNA genes in mammalian cells have hypermethylated DNA and regular nucleosomes carrying repressive histone modifications, such as H3K9me3, H4K20me3 and H3K27me3.
“Silent rRNA genes in mammalian cells are known to have hypermethylated DNA and regular nucleosomes carrying repressive histone modifications, such as H3K9me3, H4K20me3 and H3K27me3 (94,95,102,103)”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [103]
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“Silent rRNA genes in mammalian cells are known to have hypermethylated DNA and regular nucleosomes carrying repressive histone modifications, such as H3K9me3, H4K20me3 and H3K27me3 (94,95,102,103) (see (26–29) for reviews).”
BackgroundInfluentialEpigenetics of Ribosomal RNA Genes
Denisenko, O. (2022) · Biochemistry (Moscow) · doi:10.1134/s0006297922140097 · Cited by 10 · see citing works
- Authors
- Santoro, R., Li, J., & Grummt, I.
- Affiliations
- German Cancer Research Center (DE)
- Corresponding author
- Grummt, Ingrid
- Venue
- Nature Genetics
- Published
- 2002-10-07
- Volume
- 32
- Issue
- 3
- Pages
- 393-396
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2027047074
- Cited by
- 406
- References
- 1
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 8 · 2023: 13 · 2022: 10 · 2021: 9 · 2020: 18 · 2019: 16 · 2018: 15 · 2017: 18 · 2016: 19 · 2015: 19 · 2014: 24 · 2013: 20 · 2012: 17
- FWCI
- 8.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Nutrition Obesity Research Center, University of North Carolina
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- heterochromatin formation, ribosomal DNA transcription, SNF2H, SMARCA5, DNA methylation, histone deacetylase, histone H3 lysine 9 methylation, histone hypoacetylation, chromatin remodeling, epigenetic inheritance, rDNA promoter
- MeSH terms
- Bromodomain Containing Proteins, Adenosine Triphosphatases, Animals, Cell Division, Chromatin, Chromosomal Proteins, Non-Histone, DNA, DNA, Ribosomal, Heterochromatin, Histones, Models, Genetic, Precipitin Tests, RNA, Ribosomal, Time Factors, Transcription, Genetic, Transfection, 3T3 Cells, Gene Silencing, Mice
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