ArticleThe Journal of biological chemistry2004
Role of human ribosomal RNA (rRNA) promoter methylation and of methyl-CpG-binding protein MBD2 in the suppression of rRNA gene expression.
Article in The Journal of biological chemistry, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers.
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Who cites it
124 citing papers in PubMed, 206 citations in OpenAlex.
- Epigenetic changes in Alzheimer's disease: decrements in DNA methylation.Neurobiology of aging · 2010Trial
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- Cytosolic DNA inhibits rDNA transcription by retaining the RNA polymerase I transcription machinery.The EMBO journal · 2026Article
- Nucleoli-localized KANSL2 as an epigenetic regulator of ribosome biogenesis in glioblastoma cells.Communications biology · 2026Article
- ZNF16 is a nucleolar-associated protein that regulates expression of rDNA and cancer-associated genes.Biology open · 2026Article
- The cancer-testis lncRNA LINC01940 promotes gastric cancer malignant progression and chemoresistance by enhancing ribosome biogenesis via TAF15-mediated NOL11 SUMOylation.Cellular & molecular biology letters · 2025Article
- Chromosome-specific epigenetic control and transmission of ribosomal DNA arrays in Hominidae genomes.Cell genomics · 2025Article
- Multiple human enhancer RNAs contain long translated open reading frames.Genes & development · 2025Article
- ZNF16 is a nucleolar-associated protein that regulates expression of the rDNA and cancer-associated genes.bioRxiv : the preprint server for biology · 2025Article
- Kin17 promotes rDNA transcription, ribosomal biogenesis, and cortical lamination.EMBO reports · 2025Article
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- A role for the kinetochore protein, NUF2, in ribosome biogenesis.Molecular biology of the cell · 2025Article
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- Hypermethylation at 45S rDNA promoter in cancers.PloS one · 2025Article
- siRNAs, tRNAs, and rRNAs in Osteoarthritis: Biological Functions and Therapeutic Opportunities.Biologics : targets & therapy · 2025Review
- Interplay between epigenetics, senescence and cellular redox metabolism in cancer and its therapeutic implications.Redox biology · 2024Review
- Epigenetic control and inheritance of rDNA arrays.bioRxiv : the preprint server for biology · 2024Article
- The cytidine deaminase APOBEC3A regulates nucleolar function to promote cell growth and ribosome biogenesis.PLoS biology · 2024Article
- Polymerase I as a Target for Treating Neurodegenerative Disorders.Biomedicines · 2024Review
64 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The methylation status of the CpG island located within the ribosomal RNA (rRNA) promoter in human hepatocellular carcinomas and pair-matched liver tissues was analyzed by bisulfite genomic sequencing. Significant hypomethylation of methyl-CpGs in the rRNA promoter was observed in the tumor samples compared with matching normal tissues, which was consistent with the relatively high level of rRNA synthesis in rapidly proliferating tumors. To study the effect of CpG methylation on RNA polymerase I (pol I)-transcribed rRNA genes, we constructed pHrD-IRES-Luc (human rRNA promoter-luciferase reporter). In this plasmid, Kozak sequence of the pGL3-basic vector was replaced by the internal ribosome entry site (IRES) of encephalomyocarditis viral genome to optimize pol I-driven reporter gene expression. Transfection of this plasmid into HepG2 (human) cells revealed reduced pol I-driven luciferase activity with an increase in methylation density at the promoter. Markedly reduced luciferase activity in Hepa (mouse) cells compared with HepG2 (human) cells showed that pHrD-IRES-Luc is transcribed by pol I. Site-specific methylation of human rRNA promoter demonstrated that methylation of CpG at the complementary strands located in the promoter (-9, -102, -347 with respect to the +1 site) inhibited luciferase activity, whereas symmetrical methylation of a CpG in the transcribed region (+152) did not affect the promoter activity. Immunofluorescence studies showed that the methyl-CpG-binding proteins, MBD1, MBD2, MBD3, and MeCP2, are localized both in the nuclei and nucleoli of HepG2 cells. Transient overexpression of MBD2 suppressed luciferase activity specifically from the methylated rRNA promoter, whereas MBD1 and MBD3 inhibited rRNA promoter activity irrespective of the methylation status. Chromatin immunoprecipitation analysis confirmed predominant association of MBD2 with the endogenous methylated rRNA promoter, which suggests a selective role for MBD2 in the methylation-mediated inhibition of ribosomal RNA gene expression.
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