Cited by 177Genomics and Chromatin DynamicsNuclear Structure and FunctionChromosomal and Genetic Variations

Integrative genomic analysis of human ribosomal DNA

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Zentner, Gabriel E., Saiakhova, Alina, Manaenkov, Pavel, Adams, Mark D., Scacheri, Peter C.·2011·Nucleic Acids Research

Abstract

The transcription of ribosomal RNA (rRNA) is critical to life. Despite its importance, ribosomal DNA (rDNA) is not included in current genome assemblies and, consequently, genomic analyses to date have excluded rDNA. Here, we show that short sequence reads can be aligned to a genome assembly containing a single rDNA repeat. Integrated analysis of ChIP-seq, DNase-seq, MNase-seq and RNA-seq data reveals several novel findings. First, the coding region of active rDNA is contained within nucleosome-depleted open chromatin that is highly transcriptionally active. Second, histone modifications are located not only at the rDNA promoter but also at novel sites within the intergenic spacer. Third, the distributions of active modifications are more similar within and between different cell types than repressive modifications. Fourth, UBF, a positive regulator of rRNA transcription, binds to sites throughout the genome. Lastly, the insulator binding protein CTCF associates with the spacer promoter of rDNA, suggesting that transcriptional insulation plays a role in regulating the transcription of rRNA. Taken together, these analyses confirm and expand the results of previous ChIP studies of rDNA and provide novel avenues for exploration of chromatin-mediated regulation of rDNA.

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Crossref · 10.1093/nar/gkq1326

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  • Under basal conditions, a substantial proportion of the multiple rDNA repeats located on acrocentric chromosomes remain transcriptionally inactive, associated with condensed chromatin and higher levels of DNA methylation.

    “Under basal conditions, a substantial proportion of the multiple rDNA repeats located on acrocentric chromosomes remain transcriptionally inactive, being associated with condensed chromatin and higher levels of DNA methylation [176].”

    From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [176]

    The Introduction places the rDNA repeats on acrocentric chromosomes and describes silent repeats as heterochromatic and hypermethylated. The Discussion says the data include both active and inactive repeats, but also says the analysis cannot determine how many copies have a given chromatin mark. It therefore does not establish that a substantial proportion are inactive under basal conditions. (LLM, conf=0.88)

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Authors
Zentner, G. E., Saiakhova, A., Manaenkov, P., Adams, M. D., & Scacheri, P. C.
Affiliations
Case Comprehensive Cancer Center (US)
Corresponding author
Scacheri, Peter C.
Venue
Nucleic Acids Research
Published
2011-02-25
Volume
39
Issue
12
Pages
4949-4960
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
OpenAlex
W2114591008
Cited by
165
References
53
Citations by year
2026: 6 · 2025: 3 · 2024: 15 · 2023: 9 · 2022: 11 · 2021: 11 · 2020: 10 · 2019: 18 · 2018: 11 · 2017: 10 · 2016: 13 · 2015: 12 · 2014: 14 · 2013: 16 · 2012: 4
FWCI
4.67
Type
journal article
Language
en
Open access
Locations
  • Nucleic Acids Research (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Human Genome Research Institute (R01HG004722)
  • National Institute of General Medical Sciences (T32GM008613)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD056369)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
Keywords
ribosomal DNA, rRNA transcription, histone modifications, intergenic spacer, UBF, CTCF, chromatin regulation, rDNA promoter, cell type variation
MeSH terms
CCCTC-Binding Factor, Chromatin, DNA, Ribosomal, Histones, Humans, Nucleosomes, Promoter Regions, Genetic, Repressor Proteins, RNA Polymerase I, RNA, Ribosomal, Transcription, Genetic, Genome, Human, Sequence Alignment, Sequence Analysis, DNA, K562 Cells, Genomics, Pol1 Transcription Initiation Complex Proteins, Chromatin Immunoprecipitation, HEK293 Cells, High-Throughput Nucleotide Sequencing

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