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The chromatin remodeling complex NoRC targets HDAC1 to the ribosomal gene promoter and represses RNA polymerase I transcription
Open accessAbstract
Mammalian chromatin remodeling complexes are involved in both activation and repression of transcription. Here, we show that NoRC, a SNF2h- containing nucleolar chromatin remodeling complex, represses ribosomal gene transcription. NoRC-mediated rDNA silencing was alleviated by trichostatin A, indicating that histone deacetylation is causally involved in silencing. Chromatin immunoprecipitation experiments demonstrate that overexpression of TIP5, the large subunit of NoRC, mediates deacetylation of nucleosomes in the vicinity of the rDNA promoter. Protein-protein interaction assays reveal association of TIP5 with the histone deacetylase HDAC1 in vivo and in vitro. Deletion of the C-terminal PHD finger and bromodomain abolishes the interaction of TIP5 and HDAC1, and abrogates transcriptional repression. The results suggest that NoRC silences the rDNA locus by targeting the SIN3 corepressor complex to the rDNA promoter, thereby establishing a repressed chromatin structure.
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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)”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [102]
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Cited by
Sorted by citations
The Epigenetics of rRNA Genes: From Molecular to Chromosome Biology
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“NoRC silences rRNA genes by recruiting enzymes that mediate heterochromatin formation and silencing (Zhou et al. 2002; Zhou and Grummt 2005).”
BackgroundSelf-citationKi‐67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells
Bullwinkel, J., Baron‐Lühr, B., Lüdemann, A., Wohlenberg, C., Gerdes, J., & Scholzen, T. E. (2005) · Journal of Cellular Physiology · doi:10.1002/jcp.20494 · Cited by 435
“The recently discovered chromatin remodeling complex NoRC targets histone deacetylase and DNA methyltransferase activity to the rRNA gene promoter and thereby represses Pol I transcription (Santoro et al., 2002; Zhou et al., 2002).”
BackgroundChromatin remodelling at promoters suppresses antisense transcription
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Metadata
- Authors
- Zhou, Y., Santoro, R., & Grummt, I.
- Affiliations
- German Cancer Research Center (DE)
- Corresponding author
- Grummt, Ingrid
- Venue
- The EMBO Journal
- Published
- 2002-09-02
- Volume
- 21
- Issue
- 17
- Pages
- 4632-4640
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC126197
- OpenAlex
- W2045365624
- Cited by
- 234
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 9 · 2021: 5 · 2020: 8 · 2019: 6 · 2018: 11 · 2017: 6 · 2016: 12 · 2015: 9 · 2014: 10 · 2013: 12 · 2012: 15
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsches Krebsforschungszentrum
- Deutsche Forschungsgemeinschaft
- 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 › Nuclear Structure and Function
- Keywords
- norC, HDAC1, histone deacetylation, ribosomal DNA transcription, rDNA silencing, RNA polymerase I, PHD finger, bromodomain, transcriptional repression
- MeSH terms
- Bromodomain Containing Proteins, Acetylation, Animals, Cell Line, Chromatin, Chromosomal Proteins, Non-Histone, DNA, Ribosomal, Histone Deacetylases, Histones, Multienzyme Complexes, Nucleosomes, Promoter Regions, Genetic, Protein Processing, Post-Translational, Recombinant Fusion Proteins, RNA Polymerase I, Transcription, Genetic, Trans-Activators, 3T3 Cells, Protein Structure, Tertiary, Genes, rRNA, Amino Acid Motifs, Gene Silencing, Protein Interaction Mapping, Macromolecular Substances, Mice, Sin3 Histone Deacetylase and Corepressor Complex, Histone Deacetylase 1
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