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JHDM1B/FBXL10 is a nucleolar protein that represses transcription of ribosomal RNA genes
Abstract
JHDM1B is an evolutionarily conserved and ubiquitously expressed member of the JHDM (JmjC-domain-containing histone demethylase) family. Because it contains an F-box motif, this protein is also known as FBXL10 (ref. 4). With the use of a genome-wide RNAi screen, the JHDM1B worm orthologue (T26A5.5) was identified as a gene that regulates growth. In the mouse, four independent screens have identified JHDM1B as a putative tumour suppressor by retroviral insertion analysis. Here we identify human JHDM1B as a nucleolar protein and show that JHDM1B preferentially binds the transcribed region of ribosomal DNA to repress the transcription of ribosomal RNA genes. We also show that repression of ribosomal RNA genes by JHDM1B is dependent on its JmjC domain, which is necessary for the specific demethylation of trimethylated lysine 4 on histone H3 in the nucleolus. In agreement with the notion that ribosomal RNA synthesis and cell growth are coupled processes, we show a JmjC-domain-dependent negative effect of JHDM1B on cell size and cell proliferation. Because aberrant ribosome biogenesis and the disruption of epigenetic control mechanisms contribute to cellular transformation, these results, together with the low levels of JHDM1B expression found in aggressive brain tumours, suggest a role for JHDM1B in cancer development.
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“Interestingly, inactivating mutations and/or reduced expression of JmjC histone demethylases including JARID1C (Dalgliesh et al, 2010), UTX (van Haaften et al, 2009) and JHDM1B/FBXL10 (Frescas et al, 2007), occur in RCCs, multiple myeloma, glioblastoma multiforme and several other cancers.”
From The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases (2011) · cites this paper as Frescas et al, 2007
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Metadata
- Authors
- Frescas, D., Guardavaccaro, D., Bassermann, F., Koyama-Nasu, R., & Pagano, M.
- Affiliations
- New York University (US)
- Corresponding author
- Pagano, Michele
- Venue
- Nature
- Published
- 2007-11
- Volume
- 450
- Issue
- 7167
- Pages
- 309-313
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1975472671
- Cited by
- 284
- References
- 31
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 14 · 2023: 11 · 2022: 9 · 2021: 15 · 2020: 14 · 2019: 9 · 2018: 14 · 2017: 11 · 2016: 13 · 2015: 12 · 2014: 24 · 2013: 19 · 2012: 17
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- B, histone H3 lysine 4 trimethylation, ribosomal RNA gene transcription, nucleolar proteins, tumour suppressor, ribosome biogenesis, cell proliferation, cell size, epigenetic regulation, histone demethylation, carcinogenesis
- MeSH terms
- Cell Nucleolus, DNA, Ribosomal, HeLa Cells, Histones, Humans, Methylation, Nuclear Proteins, Oxidoreductases, N-Demethylating, Repressor Proteins, Transcription, Genetic, Down-Regulation, Protein Structure, Tertiary, Genes, rRNA, RNA Interference, F-Box Proteins, Cell Proliferation, Jumonji Domain-Containing Histone Demethylases
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