Quiescence-induced LncRNAs trigger H4K20 trimethylation and transcriptional silencing
Open accessAbstract
A complex network of regulatory pathways links transcription to cell growth and proliferation. Here we show that cellular quiescence alters chromatin structure by promoting trimethylation of histone H4 at lysine 20 (H4K20me3). In contrast to pericentric or telomeric regions, recruitment of the H4K20 methyltransferase Suv4-20h2 to rRNA genes and IAP elements requires neither trimethylation of H3K9 nor interaction with HP1 proteins but depends on long noncoding RNAs (lncRNAs) that interact with Suv4-20h2. Growth factor deprivation and terminal differentiation lead to upregulation of these lncRNAs, increase in H4K20me3, and chromatin compaction. The results uncover a lncRNA-mediated mechanism that guides Suv4-20h2 to specific genomic loci to establish a more compact chromatin structure in growth-arrested cells.
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This chromatin state constrains access of the transcriptional machinery to the rDNA promoter, limiting RNA Polymerase I recruitment regardless of upstream anabolic signaling.
“This chromatin state constrains access of the transcriptional machinery to the rDNA promoter, thereby limiting RNA Polymerase I recruitment regardless of the presence of upstream anabolic signaling [177].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [177]
H3K27me3 and H4K20me3 marks have been shown to be involved in rDNA silencing in mammalian cells.
“However, the levels of H3K27me3 and H4K20me3 marks, which have also been shown to be involved in rDNA silencing in mammalian cells (94,95) did not change significantly for any of the analyzed sequences (Supplementary Figure S10B and C).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [94]
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 [94]
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References 32 · Cited by 179
- Authors
- Bierhoff, H., Dammert, M. A., Brocks, D., Dambacher, S., Schotta, G., & Grummt, I.
- Affiliations
- German Cancer Research Center (DE)
- Center for Integrated Protein Science Munich (DE)
- Corresponding author
- Grummt, Ingrid
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 54
- Issue
- 4
- Pages
- 675-682
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2157334826
- Cited by
- 179
- References
- 32
- Citations by year
- 2026: 15 · 2025: 9 · 2024: 19 · 2023: 19 · 2022: 6 · 2021: 19 · 2020: 23 · 2019: 10 · 2018: 10 · 2017: 15 · 2016: 17 · 2015: 13 · 2014: 4
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- 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 › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- long non-coding RNA, H4K20 trimethylation, quiescent cells, transcriptional silencing, chromatin condensation, ribosomal DNA, growth factor deprivation, terminal differentiation, chromatin structure
- MeSH terms
- Animals, Chromatin, Gene Expression Regulation, Histones, Genes, Intracisternal A-Particle, Lysine, Methylation, Histone-Lysine N-Methyltransferase, Telomere, Genes, rRNA, Gene Silencing, NIH 3T3 Cells, Cell Proliferation, Mice, Genetic Loci, RNA, Long Noncoding
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