KAP1 controls endogenous retroviruses in embryonic stem cells
Open accessAbstract
More than forty per cent of the mammalian genome is derived from retroelements, of which about one-quarter are endogenous retroviruses (ERVs). Some are still active, notably in mice the highly polymorphic early transposon (ETn)/MusD and intracisternal A-type particles (IAP). ERVs are transcriptionally silenced during early embryogenesis by histone and DNA methylation (and reviewed in ref. 7), although the initiators of this process, which is essential to protect genome integrity, remain largely unknown. KAP1 (KRAB-associated protein 1, also known as tripartite motif-containing protein 28, TRIM28) represses genes by recruiting the histone methyltransferase SETDB1, heterochromatin protein 1 (HP1) and the NuRD histone deacetylase complex, but few of its physiological targets are known. Two lines of evidence suggest that KAP1-mediated repression could contribute to the control of ERVs: first, KAP1 can trigger permanent gene silencing during early embryogenesis, and second, a KAP1 complex silences the retrovirus murine leukaemia virus in embryonic cells. Consistent with this hypothesis, here we show that KAP1 deletion leads to a marked upregulation of a range of ERVs, in particular IAP elements, in mouse embryonic stem (ES) cells and in early embryos. We further demonstrate that KAP1 acts synergistically with DNA methylation to silence IAP elements, and that it is enriched at the 5' untranslated region (5'UTR) of IAP genomes, where KAP1 deletion leads to the loss of histone 3 lysi…
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KAP1 plays a critical role in suppressing endogenous retroviruses and has emerged as a regulator of L1s.
“KAP1 is known to play a critical role in suppressing endogenous retroviruses, and has recently emerged as a regulator of L1s as well31,40.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [31]
KAP1 has been reported to induce silencing of endogenous retroelements in part by coordinating the assembly of a HP1α-SETDB1 dependent co-repressor complex.
“KAP1 has been reported to induce silencing of endogenous retroelements31 in part by coordinating the assembly of a HP1α-SETDB1 dependent co-repressor complex32.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [31]
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- Authors
- Rowe, H. M., Jakobsson, J., Mesnard, D., Rougemont, J., Reynard, S., Aktas, T., Maillard, P. V., Layard-Liesching, H., Verp, S., Marquis, J., Spitz, F., Constam, D. B., & Trono, D.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Lund University (SE)
- European Molecular Biology Laboratory (DE)
- Corresponding author
- Trono, Didier
- ORCID
- Venue
- Nature
- Published
- 2010-01
- Volume
- 463
- Issue
- 7278
- Pages
- 237-240
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2059919630
- Cited by
- 874
- References
- 3
- Citations by year
- 2026: 62 · 2025: 58 · 2024: 61 · 2023: 68 · 2022: 72 · 2021: 71 · 2020: 67 · 2019: 40 · 2018: 46 · 2017: 42 · 2016: 54 · 2015: 50 · 2014: 44 · 2013: 42 · 2012: 38
- FWCI
- 17.84
- Type
- journal article
- Language
- en
- Open access
- green
- infoscience.epfl.ch
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Lund University Publications (Lund University) (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Vetenskapsrådet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- KAP1, TRIM28, endogenous retroviruses, intracisternal A-particle, embryonic stem cells, early embryonic development, epigenetic silencing, DNA methylation, histone methylation, SETDB1, heterochromatin, mouse embryo, genome stability
- MeSH terms
- Tripartite Motif-Containing Protein 28, Acetylation, Animals, Embryo, Mammalian, Fibroblasts, Histones, Genes, Intracisternal A-Particle, Lysine, Methylation, Leukemia Virus, Murine, Nuclear Proteins, Promoter Regions, Genetic, Repressor Proteins, Genes, Reporter, DNA Methylation, Endogenous Retroviruses, 5' Untranslated Regions, Gene Silencing, Green Fluorescent Proteins, Mice, Embryonic Stem Cells
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