The HUSH complex cooperates with TRIM28 to repress young retrotransposons and new genes
Open accessAbstract
Retrotransposons encompass half of the human genome and contribute to the formation of heterochromatin, which provides nuclear structure and regulates gene expression. Here, we asked if the human silencing hub (HUSH) complex is necessary to silence retrotransposons and whether it collaborates with TRIM28 and the chromatin remodeler ATRX at specific genomic loci. We show that the HUSH complex contributes to de novo repression and DNA methylation of an SVA retrotransposon reporter. By using naïve versus primed mouse pluripotent stem cells, we reveal a critical role for the HUSH complex in naïve cells, implicating it in programming epigenetic marks in development. Although the HUSH component FAM208A binds to endogenous retroviruses (ERVs) and long interspersed element-1s (LINE-1s or L1s), it is mainly required to repress evolutionarily young L1s (mouse-specific lineages <5 million years old). TRIM28, in contrast, is necessary to repress both ERVs and young L1s. Genes co-repressed by TRIM28 and FAM208A are evolutionarily young, or exhibit tissue-specific expression, are enriched in young L1s, and display evidence for regulation through LTR promoters. Finally, we demonstrate that the HUSH complex is also required to repress L1 elements in human cells. Overall, these data indicate that the HUSH complex and TRIM28 co-repress young retrotransposons and new genes rewired by retrotransposon noncoding DNA.
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The same chromatin repressors are involved in epigenetic silencing of endogenous retroviruses.
“The same chromatin repressors are involved in epigenetic silencing of endogenous retroviruses39.”
From Locus for severity implicates CNS resilience in progression of multiple sclerosis (2023) · cites this paper as [39]
The Discussion (Figure 7 model; page unavailable) says TRIM28 is required to repress endogenous retroviruses, and FAM208A also binds to them. It explicitly says FAM208A is not required for their repression, so the paper does not support the claim that both repressors silence endogenous retroviruses. (LLM, conf=0.88)
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- Authors
- Robbez-Masson, L., Tie, C. H. C., Conde, L., Tunbak, H., Husovsky, C., Tchasovnikarova, I. A., Timms, R. T., Herrero, J., Lehner, P. J., & Rowe, H. M.
- Affiliations
- University College London (GB)
- University of Cambridge (GB)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2018-05-04
- Volume
- 28
- Issue
- 6
- Pages
- 836-845
- ISSN
- 1088-9051 (ISSN-L)
- 1549-5469
- PMC
- PMC5991525
- OpenAlex
- W2801545642
- Cited by
- 221
- References
- 5
- Citations by year
- 2026: 23 · 2025: 31 · 2024: 26 · 2023: 33 · 2022: 30 · 2021: 31 · 2020: 22 · 2019: 14 · 2018: 11
- Type
- posted content
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by
- Locations
- Genome Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- Sir Henry Dale Fellowship
- Wellcome Trust
- Royal Society (101200/Z/13/Z)
- Wellcome Trust Principal Research Fellowship (101835/Z/13/Z)
- Topics
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- HUSH complex, TRIM28, retrotransposon silencing, LINE-1, SVA retrotransposon, ATRX, DNA methylation, naive pluripotent stem cells, endogenous retroviruses, LTR promoter, heterochromatin, epigenetic regulation
- MeSH terms
- Tripartite Motif-Containing Protein 28, Animals, Heterochromatin, Humans, Nuclear Proteins, Promoter Regions, Genetic, Genome, Human, Retroelements, DNA Methylation, Endogenous Retroviruses, Long Interspersed Nucleotide Elements, Mice
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