Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin
Abstract
Here, we show a role for the RB1 family proteins in directing full heterochromatin formation. Mouse embryonic fibroblasts that are triply deficient for RB1 (retinoblastoma 1), RBL1 (retinoblastoma-like 1) and RBL2 (retinoblastoma-like 2) - known as TKO cells - show a marked genomic instability, which is coincidental with decreased DNA methylation, increased acetylation of histone H3 and decreased tri-methylation of histone H4 at lysine 20 (H4K20). Chromatin immunoprecipitation showed that H4K20 tri-methylation was specifically decreased at pericentric and telomeric chromatin. These defects are independent of E2F family function. Indeed, we show a direct interaction between the RB1 proteins and the H4K20 tri-methylating enzymes Suv4-20h1 and Suv4-20h2, indicating that the RB1 family has a role in controlling H4K20 tri-methylation by these histone methyltransferases. These observations indicate that the RB1 family is involved in maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin, linking tumour suppression and the epigenetic definition of chromatin.
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RB may help maintain genomic stability by regulating expression of and associating with chromatin remodelling complexes, particularly at centromeres and telomeres.
“RB might help maintain genomic stability by regulating the expression of, and associating with, chromatin remodelling complexes, thereby regulating chromatin structure, in particular at centromeres and telomeres109–112.”
From Cellular mechanisms of tumour suppression by the retinoblastoma gene (2008) · cites this paper as [110]
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“The role of the RB1 family in directing heterochromatin formation may be related to the previously described role of RB1 in the formation of the so-called senescence-associated heterochromatic foci (SAHF”
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- Authors
- Gonzalo, S., García-Cao, M., Fraga, M. F., Schotta, G., Peters, A. H. F. M., Cotter, S. E., Eguía, R., Dean, D. C., Esteller, M., Jenuwein, T., & Blasco, M. A.
- Affiliations
- Spanish National Cancer Research Centre (ES)
- Research Institute of Molecular Pathology (AT)
- Washington University in St. Louis (US)
- University of Louisville (US)
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2005-03-06
- Volume
- 7
- Issue
- 4
- Pages
- 420-428
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2073224213
- Cited by
- 343
- References
- 6
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 9 · 2023: 9 · 2022: 16 · 2021: 13 · 2020: 7 · 2019: 18 · 2018: 14 · 2017: 16 · 2016: 12 · 2015: 10 · 2014: 17 · 2013: 17 · 2012: 25
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- retinoblastoma protein, RBL1, RBL2, constitutive heterochromatin, histone methyltransferase, genomic instability, DNA methylation, histone H3 acetylation, telomeric chromatin, tumor suppression
- MeSH terms
- Animals, Fibroblasts, Heterochromatin, Histones, Methylation, Models, Biological, Nuclear Proteins, Proteins, Retinoblastoma Protein, Mice, Knockout, DNA Methylation, Retinoblastoma-Like Protein p130, Retinoblastoma-Like Protein p107, Mice
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