ArticleNature2010
Proviral silencing in embryonic stem cells requires the histone methyltransferase ESET.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 492 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
492 citing papers in PubMed, 804 citations in OpenAlex.
- A two-hit mechanism triggers autoimmune hair loss.Nature · 2026Article
- The CTNNB1-TRIM28 complex governs hormone-induced RNA polymerase II dynamics in kidney epithelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Innate Immune Reprogramming Mediated by Endogenous Retroelement Dysregulation Drives Multiple Sclerosis Progression.Annals of clinical and translational neurology · 2026Article
- Recurrent ZC3H18 mutations stabilize oncogenic endogenous retroviral RNA.Cell reports · 2026Article
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- Dynamic regulation of H3K9 dimethylation drives mouse minor zygotic genome activation.Nature structural & molecular biology · 2026Article
- Ice-free vitrification of embryos and its impact on post-warming outcomes.Scientific reports · 2026Article
- Loss of maternal PADI6 disrupts DNA methylation and genomic imprinting maintenance in late preimplantation mouse embryos.Epigenetics & chromatin · 2026Article
- SETDB1 promotes gastric cancer progression via UPR and mTOR pathway.Cancer cell international · 2026Article
- SETDB1 and HUSH modulate Xist RNA levels during establishment of X chromosome inactivation.Nature communications · 2026Article
- The Many Faces of SetDB1.Epigenomes · 2026Review
- Roles of TIF1β in Leukemic Stem Cell Through SETDB1-Dependent and Independent Mechanisms.Cancer science · 2026Review
- Hat1 Orchestrates Heterochromatin Inheritance by Regulating Localization of H3K9 Methyltransferases.bioRxiv : the preprint server for biology · 2026Article
- Transcriptional competence defines the heterochromatin nucleating potential of isolated MSR units.Nature communications · 2026Article
- Human Endogenous Retroviruses and Epigenetic Regulators Are Dysregulated in Beckwith-Wiedemann Syndrome.Current issues in molecular biology · 2026Article
- One-Step Multiplex PCR Reveals Selective Activation of Immunostimulatory Human Endogenous Retroviruses and Epigenetic Imbalance in Systemic Lupus Erythematosus.International journal of molecular sciences · 2026Article
- The role of KRAB zinc-finger proteins in expanding the domestication potential of transposable elements.Nature genetics · 2026Review
- Article
- Epigenetic mechanisms of retroviral regulation: a comparative review.Epigenetics & chromatin · 2026Review
- Heterochromatin boundaries maintain centromere position, size and number.Nature structural & molecular biology · 2026Article
432 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Endogenous retroviruses (ERVs), retrovirus-like elements with long terminal repeats, are widely dispersed in the euchromatic compartment in mammalian cells, comprising approximately 10% of the mouse genome. These parasitic elements are responsible for >10% of spontaneous mutations. Whereas DNA methylation has an important role in proviral silencing in somatic and germ-lineage cells, an additional DNA-methylation-independent pathway also functions in embryonal carcinoma and embryonic stem (ES) cells to inhibit transcription of the exogenous gammaretrovirus murine leukaemia virus (MLV). Notably, a recent genome-wide study revealed that ERVs are also marked by histone H3 lysine 9 trimethylation (H3K9me3) and H4K20me3 in ES cells but not in mouse embryonic fibroblasts. However, the role that these marks have in proviral silencing remains unexplored. Here we show that the H3K9 methyltransferase ESET (also called SETDB1 or KMT1E) and the Krüppel-associated box (KRAB)-associated protein 1 (KAP1, also called TRIM28) are required for H3K9me3 and silencing of endogenous and introduced retroviruses specifically in mouse ES cells. Furthermore, whereas ESET enzymatic activity is crucial for HP1 binding and efficient proviral silencing, the H4K20 methyltransferases Suv420h1 and Suv420h2 are dispensable for silencing. Notably, in DNA methyltransferase triple knockout (Dnmt1(-/-)Dnmt3a(-/-)Dnmt3b(-/-)) mouse ES cells, ESET and KAP1 binding and ESET-mediated H3K9me3 are maintained and ERVs are minimally derepressed. We propose that a DNA-methylation-independent pathway involving KAP1 and ESET/ESET-mediated H3K9me3 is required for proviral silencing during the period early in embryogenesis when DNA methylation is dynamically reprogrammed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.