ArticleGenes & development2014
Setdb1 is required for germline development and silencing of H3K9me3-marked endogenous retroviruses in primordial germ cells.
Article in Genes & development, 2014. 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 168 papers.
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Who cites it
168 citing papers in PubMed, 270 citations in OpenAlex.
- MORC1 coordinates TRIM28 interaction and nuclear condensate formation for transposon silencing.iScience · 2026Article
- Viral mimicry escape as a necessary feature of malignant transformation.Nature reviews. Cancer · 2026Review
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- Transposable element regulation in mammalian germ cells and other contexts: multilayered repression, fertility, and regulated activation.Epigenomics · 2026Review
- In mice, a population of male germ cells show characteristics of non-apoptotic cell death during G0 arrest.bioRxiv : the preprint server for biology · 2026Article
- Histone modification cross-talk: analytical tools and molecular mechanisms.The Biochemical journal · 2026Review
- Reprogramming the inactive X chromosome: dynamics and insights from the germline.Biochemical Society transactions · 2026Review
- Heterochromatin boundaries maintain centromere position, size and number.Nature structural & molecular biology · 2026Article
- Cell density-dependent nuclear-cytoplasmic shuttling of SETDB1 integrates with Hippo signaling to regulate YAP1-mediated transcription.FEBS letters · 2026Article
- Functional Analyses of Histone Methyltransferases in Sea Lamprey Embryos Undergoing Programmed DNA Elimination.bioRxiv : the preprint server for biology · 2026Article
- Gonocytes in Transition: Establishing the Male Germline Identity.Advances in experimental medicine and biology · 2026Review
- Endogenous retrovirus IAP forms virus-like particles and traffics across the maternal-fetal barrier.bioRxiv : the preprint server for biology · 2025Article
- Stage-dependent dual mechanisms of MORC2 in retrotransposon silencing and sex chromosome inactivation in germ cells.Nucleic acids research · 2025Article
- DNA methylation dictates histone modifications in developing male germ cells in the mouse.Nucleic acids research · 2025Article
- Sex-specific expression and function of TRIM28 during mouse primordial germ differentiation.iScience · 2025Article
- Microglial deficiency in the ATRX chromatin remodeler elicits a viral mimicry immune response that impacts neuronal function and behavior.PLoS biology · 2025Article
- UHRF2 mediates resistance to DNA methylation reprogramming in primordial germ cells.Nature communications · 2025Article
- The SWI/SNF-related protein SMARCA3 is a histone H3K23 ubiquitin ligase that regulates H3K9me3 in cancer.Molecular cell · 2025Article
- ATF7IP/SETDB1-mediated epigenetic programming regulates thymic homing and T lymphopoiesis of hematopoietic progenitors during embryogenesis.Nature communications · 2025Article
- Exploring transposable elements: new horizons in cancer diagnostics and therapeutics.Mobile DNA · 2025Review
108 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Transcription of endogenous retroviruses (ERVs) is inhibited by de novo DNA methylation during gametogenesis, a process initiated after birth in oocytes and at approximately embryonic day 15.5 (E15.5) in prospermatogonia. Earlier in germline development, the genome, including most retrotransposons, is progressively demethylated. Young ERVK and ERV1 elements, however, retain intermediate methylation levels. As DNA methylation reaches a low point in E13.5 primordial germ cells (PGCs) of both sexes, we determined whether retrotransposons are marked by H3K9me3 and H3K27me3 using a recently developed low-input ChIP-seq (chromatin immunoprecipitation [ChIP] combined with deep sequencing) method. Although these repressive histone modifications are found predominantly on distinct genomic regions in E13.5 PGCs, they concurrently mark partially methylated long terminal repeats (LTRs) and LINE1 elements. Germline-specific conditional knockout of the H3K9 methyltransferase SETDB1 yields a decrease of both marks and DNA methylation at H3K9me3-enriched retrotransposon families. Strikingly, Setdb1 knockout E13.5 PGCs show concomitant derepression of many marked ERVs, including intracisternal A particle (IAP), ETn, and ERVK10C elements, and ERV-proximal genes, a subset in a sex-dependent manner. Furthermore, Setdb1 deficiency is associated with a reduced number of male E13.5 PGCs and postnatal hypogonadism in both sexes. Taken together, these observations reveal that SETDB1 is an essential guardian against proviral expression prior to the onset of de novo DNA methylation in the germline.
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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.