Active human nucleolar organizer regions are interspersed with inactive rDNA repeats in normal and tumor cells
Open accessAbstract
Aim The synthesis of rRNA is a key determinant of normal and malignant cell growth and subject to epigenetic regulation. Yet, the epigenomic features of rDNA arrays clustered in nucleolar organizer regions are largely unknown. We set out to explore for the first time how DNA methylation is distributed on individual rDNA arrays. Materials & methods Here we combined immunofluorescence detection of DNA modifications with fluorescence hybridization of single DNA fibers, metaphase immuno-FISH and methylation-sensitive restriction enzyme digestions followed by Southern blot. Results We found clustering of both hypomethylated and hypermethylated repeat units and hypermethylation of noncanonical rDNA in IMR90 fibroblasts and HCT116 colorectal carcinoma cells. Surprisingly, we also found transitions between hypo- and hypermethylated rDNA repeat clusters on single DNA fibers. Conclusion Collectively, our analyses revealed co-existence of different epialleles on individual nucleolar organizer regions and showed that epi-combing is a valuable approach to analyze epigenomic patterns of repetitive DNA.
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Within active NORs, some rRNA genes can be silent.
“Moreover, within the active NORs, some rRNA genes can be silent (19,20).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [20]
Approximately 20-30% of rDNA repeats in human cell lines are palindromic and noncanonical.
“For instance, approximately 20–30% of rDNA repeats in human cell lines are palindromic and noncanonical (20,25).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [20]
Our findings parallel with the results revealing the coexistence of methylated and unmethylated rDNA units within the same cluster in human cells.
“Our findings parallel with the results revealing the coexistence of methylated and unmethylated rDNA units within the same cluster using FISH and immunostaining of single DNA fibers in human cells (20).”
From Impaired function of rDNA transcription initiation machinery leads to derepression of ribosomal genes with insertions of R2 retrotransposon (2022) · cites this paper as [20]
Cites
Direct detection of DNA methylation during single-molecule, real-time sequencing
Flusberg, B. A., Webster, D. R., Lee, J. H., Travers, K. J., Olivares, E. C., Clark, T. A., Korlach, J., & Turner, S. W. (2010) · Nature Methods · doi:10.1038/nmeth.1459 · Cited by 1,460 · see citing works
Epigenetic regulation of TTF-I-mediated promoter-terminator interactions of rRNA genes
Németh, A., Guibert, S., Tiwari, V. K., Ohlsson, R., & Längst, G. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.57 · Cited by 94 · see citing works
Self-citationStancheva, I., Lucchini, R., Koller, T., & Sogo, J. M. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.9.1727 · Cited by 51 · see citing works
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Fefelova, E. A., Pleshakova, I. M., Mikhaleva, E. A., Pirogov, S. A., Poltorachenko, V. A., Abramov, Y. A., Romashin, D. D., Shatskikh, A. S., Blokh, R. S., Gvozdev, V. A., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkab1276 · Cited by 15 · see citing works
- Authors
- Zillner, K., Komatsu, J., Filarsky, K., Kalepu, R., Bensimon, A., & Németh, A.
- Affiliations
- University of Regensburg (DE)
- Genomic Vision (France) (FR)
- German Cancer Research Center (DE)
- University Hospital Ulm (DE)
- Venue
- Epigenomics
- Publisher
- Informa UK Limited
- Published
- 2015-06
- Volume
- 7
- Issue
- 3
- Pages
- 363-378
- ISSN
- 1750-1911 (ISSN-L)
- 1750-192X
- OpenAlex
- W1908715577
- Cited by
- 28
- References
- 3
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 4
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Epigenomics (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB960)
- Bavarian Elite Network
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- nucleolar organizer regions, rDNA repeats, DNA methylation, epigenetic regulation, ribosomal RNA synthesis, epialleles, colorectal cancer, fibroblasts
- MeSH terms
- DNA, Ribosomal, Female, Humans, Male, Nucleolus Organizer Region, Repetitive Sequences, Nucleic Acid, Genome, Human, DNA Methylation, Genes, rRNA, Epigenesis, Genetic
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