ArticleThe Journal of biological chemistry2010
Repression of retrotransposal elements in mouse embryonic stem cells is primarily mediated by a DNA methylation-independent mechanism.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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The trial behind it
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Who cites it
54 citing papers in PubMed, 81 citations in OpenAlex.
- Endogenous retrovirus IAP forms virus-like particles and traffics across the maternal-fetal barrier.bioRxiv : the preprint server for biology · 2025Article
- Reactivation of retrotransposable elements is associated with environmental stress and ageing.Nature reviews. Genetics · 2025Review
- Activation of endogenous retroviruses characterizes the maternal-fetal interface in the BTBR mouse model of autism spectrum disorder.Scientific reports · 2025Article
- Epigenome-wide methylation analysis shows phosphonoethylamine alleviates aberrant DNA methylation in NASH caused by Pcyt2 deficiency.PloS one · 2025Article
- RNA-mediated heterochromatin formation at repetitive elements in mammals.The EMBO journal · 2023Review
- Transcriptional Regulation of Endogenous Retroviruses and Their Misregulation in Human Diseases.International journal of molecular sciences · 2022Review
- Review
- Characterization of DNA methylation and promoter activity of long terminal repeat elements of feline endogenous retrovirus RDRS C2a.Virus genes · 2022Article
- The DNMT1 inhibitor GSK-3484862 mediates global demethylation in murine embryonic stem cells.Epigenetics & chromatin · 2021Article
- Dnmt1 has de novo activity targeted to transposable elements.Nature structural & molecular biology · 2021Article
- Drug Response-Related DNA Methylation Changes in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder.Frontiers in neuroscience · 2021Review
- Genome-wide analysis in the mouse embryo reveals the importance of DNA methylation for transcription integrity.Nature communications · 2020Article
- SETDB1-Mediated Silencing of Retroelements.Viruses · 2020Review
- The diverse roles of DNA methylation in mammalian development and disease.Nature reviews. Molecular cell biology · 2019Review
- Regulation of transposable elements by DNA modifications.Nature reviews. Genetics · 2019Review
- Wnt/β-catenin signaling pathway safeguards epigenetic stability and homeostasis of mouse embryonic stem cells.Scientific reports · 2019Article
- A somatic role for the histone methyltransferase Setdb1 in endogenous retrovirus silencing.Nature communications · 2018Article
- High expression of Endogenous Retroviruses from intrauterine life to adulthood in two mouse models of Autism Spectrum Disorders.Scientific reports · 2018Article
- Oct4 regulates DNA methyltransferase 1 transcription by direct binding of the regulatory element.Cellular & molecular biology letters · 2018Article
- An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells.Cell stem cell · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
In defense of deleterious retrotransposition of intracisternal A particle (IAP) elements, IAP loci are heavily methylated and silenced in mouse somatic cells. To determine whether IAP is also repressed in pluripotent stem cells by DNA methylation, we examined IAP expression in demethylated mouse embryonic stem cells (mESCs) and epiblast-derived stem cells. Surprisingly, in demethylated ESC cultures carrying mutations of DNA methyltransferase I (Dnmt1), no IAP transcripts and proteins are detectable in undifferentiated Oct4(+) ESCs. In contrast, approximately 3.6% of IAP-positive cells are detected in Oct4(-) Dnmt1(-/-) cells, suggesting that the previously observed increase in IAP transcripts in the population of Dnmt1(-/-) ESCs could be accounted for by this subset of Oct4(-) Dnmt1(-/-) ESCs undergoing spontaneous differentiation. Consistent with this possibility, a dramatic increase of IAP mRNA (>100-fold) and protein expression was observed in Dnmt1(-/-) ESC cultures upon induction of differentiation through the withdrawal of leukemia-inhibitory factor for 6 or more days. Interestingly, both mRNAs and proteins of IAP can be readily detected in demethylated Oct4(+) epiblast-derived stem cells as well as differentiated mouse embryo fibroblasts, neurons, and glia upon conditional Dnmt1 gene deletion. These data suggest that mESCs are a unique stem cell type possessing a DNA methylation-independent IAP repression mechanism. This methylation-independent mechanism does not involve Dicer-mediated action of microRNAs or RNA interference because IAP expression remains repressed in Dnmt1(-/-); Dicer(-/-) double mutant ESCs. We suggest that mESCs possess a unique DNA methylation-independent mechanism to silence retrotransposons to safeguard genome stability while undergoing rapid cell proliferation for self-renewal.
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