The chromatin remodeling complex NuRD establishes the poised state of rRNA genes characterized by bivalent histone modifications and altered nucleosome positions
Open accessAbstract
rRNA genes (rDNA) exist in two distinct epigenetic states, active promoters being unmethylated and marked by euchromatic histone modifications, whereas silent ones are methylated and exhibit heterochromatic features. Here we show that the nucleosome remodeling and deacetylation (NuRD) complex establishes a specific chromatin structure at rRNA genes that are poised for transcription activation. The promoter of poised rRNA genes is unmethylated, associated with components of the preinitiation complex, marked by bivalent histone modifications and covered by a nucleosome in the "off" position, which is refractory to transcription initiation. Repression of rDNA transcription in growth-arrested and differentiated cells correlates with elevated association of NuRD and increased levels of poised rRNA genes. Reactivation of transcription requires resetting the promoter-bound nucleosome into the "on" position by the DNA-dependent ATPase CSB (Cockayne syndrome protein B). The results uncover a unique mechanism by which ATP-dependent chromatin remodeling complexes with opposing activities establish a specific chromatin state and regulate transcription.
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Repressive complexes such as the NuRD complex establish and maintain the poised or silenced state of rRNA genes.
“In parallel, repressive complexes such as the nucleosome remodeling and deacetylase (NuRD) complex are biologically known to establish and maintain the poised or silenced state of rRNA genes [180].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [180]
The paper states that CHD4/NuRD establishes the poised state of rRNA genes. In the Discussion (page unavailable), it distinguishes this from the methylated silent state, which it says is established by NoRC. It does not establish that NuRD maintains either state, so the claim overextends its role. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSilent 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 [95]
The Discussion describes silent rRNA genes as methylated and heterochromatic. In “CHD4/NuRD and CSB Cooperate in Pol I Transcription Activation,” H4K20me3 and H3K27me3 are associated with the silent-gene nucleosome position, but H3K9me3 occurs at both active and silent positions. The cited passages do not establish that silent genes have regular nucleosomes. (LLM, conf=0.88)
Experimental — accuracy not yet measuredH3K27me3 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 [95]
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References 25 · Cited by 124
- Authors
- Xie, W., Ling, T., Zhou, Y., Feng, W., Zhu, Q., Stunnenberg, H. G., Grummt, I., & Tao, W.
- Affiliations
- Peking University (CN)
- German Cancer Research Center (DE)
- Nijmegen Centre for Molecular Life Sciences, 6500 HB, Nijmegen, The Netherlands
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-05-08
- Volume
- 109
- Issue
- 21
- Pages
- 8161-8166
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3361413
- OpenAlex
- W2120728889
- Cited by
- 124
- References
- 25
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 14 · 2020: 7 · 2019: 8 · 2018: 8 · 2017: 10 · 2016: 13 · 2015: 9 · 2014: 4 · 2013: 21 · 2012: 3
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- National Natural Science Foundation of China (30871377, 31171255, 31071116)
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- ribosomal DNA, NuRD complex, chromatin remodeling, bivalent histone modifications, nucleosome positioning, DNA methylation, transcriptional repression, transcriptional activation, CSB, ATP-dependent chromatin remodeling, preinitiation complex, growth arrest, cell differentiation
- MeSH terms
- Poly-ADP-Ribose Binding Proteins, Adenosine Triphosphatases, Animals, Cell Differentiation, Chromatin, DNA Helicases, DNA-Binding Proteins, Histones, Nucleosomes, RNA Polymerase I, RNA, Ribosomal, Transcription Factors, Transcriptional Activation, Genes, rRNA, NIH 3T3 Cells, Epigenesis, Genetic, DNA Repair Enzymes, Mice, Mi-2 Nucleosome Remodeling and Deacetylase Complex
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