An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences
Open accessAbstract
Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments. We generated a mutant mouse strain carrying an F832A mutation in Rb1 that is defective for recruitment to repetitive sequences. Loss of pRB-EZH2 complexes from repeats disperses H3K27me3 from these genomic locations and permits repeat expression. Consistent with maintenance of H3K27me3 at the Hox clusters, these mice are developmentally normal. However, susceptibility to lymphoma suggests that pRB-EZH2 recruitment to repetitive elements may be cancer relevant.
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Loss of heterochromatin factors reduces heterochromatin at retrotransposons and allows their transcriptional derepression.
“Loss of these factors reduces heterochromatin at retrotransposons and allows their transcriptional derepression26, 29, 31, 33–35.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [29]
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References 53 · Cited by 167
- Authors
- Ishak, C. A., Marshall, A. E., Passos, D. T., White, C. R., Kim, S. J., Cecchini, M. J., Ferwati, S., MacDonald, W. A., Howlett, C. J., Welch, I. D., Rubin, S. M., Mann, M. R. W., & Dick, F. A.
- Affiliations
- Western University (CA)
- University of Pittsburgh (US)
- University of British Columbia (CA)
- University of California, Santa Cruz (US)
- Corresponding author
- Dick, Frederick A.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 64
- Issue
- 6
- Pages
- 1074-1087
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC5340194
- OpenAlex
- W2552764510
- Cited by
- 167
- References
- 53
- Citations by year
- 2026: 4 · 2025: 23 · 2024: 15 · 2023: 17 · 2022: 20 · 2021: 20 · 2020: 21 · 2019: 21 · 2018: 14 · 2017: 11 · 2016: 1
- FWCI
- 8.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Scholarship@Western (Western University) (submittedVersion)
- Funders
- NSERC
- WORLDiscoveries
- OGS
- CIHR (MOP-89765, MOP-64253)
- 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
- retinoblastoma protein, E2F1, EZH2, repetitive DNA, heterochromatin, LINE-1 elements, endogenous retroviruses, satellite DNA, transposable elements, H3K27me3, lymphoma susceptibility, Hox gene clusters, epigenetic regulation
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, Animals, Fibroblasts, Carcinoma, Hepatocellular, Histones, Liver Neoplasms, Lymphoma, Mesentery, Mutation, Protein Binding, Repetitive Sequences, Nucleic Acid, Splenic Neoplasms, Survival Analysis, Retinoblastoma Protein, Genetic Predisposition to Disease, Gene Silencing, E2F1 Transcription Factor, Mice, Primary Cell Culture
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