A LINE-1 retrotransposon promotes SEMA3C expression as a cis-regulatory enhancer to sustain breast cancer stem cell survival
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE296921 | GEO | 2026/03/01
REPOSITORIES: GEO
Similar Datasets
Project description:The disinhibition of transposon elements (TEs) is a significant threat to male reproduction, particularly during the delicate process of spermatogenesis. Here we identify that Death associated protein 6 (Daxx), a potent transcription repressor and an H3.3 chaperone essential for the TEs silencing during spermatogenesis. DAXX-deficient mouse display delayed meiotic progression, reduced production of spermatids, deformed spermatozoa and age-dependent decline in male fertility. We demonstrate that young long-interspersed nuclear elements (LINE1) and endogenous retroviral elements (ERVs) subfamilies, were upregulated in meiotic spermatocytes of Daxx null testes. Further study found that the Daxx mutant meiotic cells exhibit DNA hypomethylation in TEs. In summary, we have identified DAXX as a previously unknown key regulator of spermatogenesis that may function as an epigenetic regulator to silence young LINE1 by DNA methylation.
2025-04-01 | GSE293055 | GEO
Project description:Transposable elements (TEs) are mobile sequences that engender widespread mutations and thus are a major hazard that must be silenced. The most abundant active class of TEs in mammalian genomes is long interspersed element class 1 (LINE1). Here, we report that LINE1 transposition is suppressed in the male germline by transcription factors encoded by a rapidly evolving X-linked homeobox gene cluster. LINE1 transposition is repressed by many members of this RHOX transcription factor family, including those with different patterns of expression during spermatogenesis. One family member—RHOX10—suppresses LINE1 transposition during fetal development in vivo when the germline would otherwise be susceptible to LINE1 activation because of epigenetic reprogramming. We provide evidence that RHOX10 suppresses LINE transposition by inducing Piwil2, which encodes a key component in the Piwi-interacting (pi) RNA pathway that protects against TEs. The ability of RHOX transcription factors to suppress LINE1 is conserved in humans, but is lost in RHOXF2 mutants from several infertile human patients, raising the possibility that loss of RHOXF2 causes human infertility by allowing uncontrolled LINE1 expression in the germline. Together, our results support a model in which the Rhox gene cluster is in an evolutionary arms race with TEs, resulting in expansion of the Rhox gene cluster to suppress TEs in different biological contexts.
2021-05-20 | GSE160600 | GEO
Project description:Early mammalian development entails widespread epigenome remodeling, including DNA methylation erasure and reacquisition, which facilitates developmental competence. To uncover the mechanisms that orchestrate global and focal DNA methylation (DNAme) dynamics, we coupled a single-cell ratiometric DNAme reporter with unbiased CRISPR screening. We identify key genes and regulatory pathways that drive developmental DNA hypomethylation, and characterise roles for Cop1 and Dusp6. We also identify Dppa2 and Dppa4 as essential safeguards of focal epigenetic states during (re)programming phases. In their absence, developmental genes and evolutionary young LINE1 elements lose H3K4me3 and gain ectopic de novo DNA methylation. Consequently, lineage-associated genes (and LINE1) acquire a repressive epigenetic memory in pluripotent cells, which renders them incompetent for activation during future lineage-specification. Dppa2/4 thereby sculpt a permissive epigenome for development by targeting H3K4me3 to counteract de novo methylation during (re)programming; a function that has been co-opted by evolutionary young LINE1 to evade epigenetic decommissioning.
2020-05-28 | GSE146862 | GEO
Project description:Early mammalian development entails widespread epigenome remodeling, including DNA methylation erasure and reacquisition, which facilitates developmental competence. To uncover the mechanisms that orchestrate global and focal DNA methylation (DNAme) dynamics, we coupled a single-cell ratiometric DNAme reporter with unbiased CRISPR screening. We identify key genes and regulatory pathways that drive developmental DNA hypomethylation, and characterise roles for Cop1 and Dusp6. We also identify Dppa2 and Dppa4 as essential safeguards of focal epigenetic states during (re)programming phases. In their absence, developmental genes and evolutionary young LINE1 elements lose H3K4me3 and gain ectopic de novo DNA methylation. Consequently, lineage-associated genes (and LINE1) acquire a repressive epigenetic memory in pluripotent cells, which renders them incompetent for activation during future lineage-specification. Dppa2/4 thereby sculpt a permissive epigenome for development by targeting H3K4me3 to counteract de novo methylation during (re)programming; a function that has been co-opted by evolutionary young LINE1 to evade epigenetic decommissioning.
2020-05-28 | GSE146861 | GEO
Project description:Early mammalian development entails widespread epigenome remodeling, including DNA methylation erasure and reacquisition, which facilitates developmental competence. To uncover the mechanisms that orchestrate global and focal DNA methylation (DNAme) dynamics, we coupled a single-cell ratiometric DNAme reporter with unbiased CRISPR screening. We identify key genes and regulatory pathways that drive developmental DNA hypomethylation, and characterise roles for Cop1 and Dusp6. We also identify Dppa2 and Dppa4 as essential safeguards of focal epigenetic states during (re)programming phases. In their absence, developmental genes and evolutionary young LINE1 elements lose H3K4me3 and gain ectopic de novo DNA methylation. Consequently, lineage-associated genes (and LINE1) acquire a repressive epigenetic memory in pluripotent cells, which renders them incompetent for activation during future lineage-specification. Dppa2/4 thereby sculpt a permissive epigenome for development by targeting H3K4me3 to counteract de novo methylation during (re)programming; a function that has been co-opted by evolutionary young LINE1 to evade epigenetic decommissioning.
2020-05-28 | GSE146860 | GEO
Project description:Early mammalian development entails widespread epigenome remodeling, including DNA methylation erasure and reacquisition, which facilitates developmental competence. To uncover the mechanisms that orchestrate global and focal DNA methylation (DNAme) dynamics, we coupled a single-cell ratiometric DNAme reporter with unbiased CRISPR screening. We identify key genes and regulatory pathways that drive developmental DNA hypomethylation, and characterise roles for Cop1 and Dusp6. We also identify Dppa2 and Dppa4 as essential safeguards of focal epigenetic states during (re)programming phases. In their absence, developmental genes and evolutionary young LINE1 elements lose H3K4me3 and gain ectopic de novo DNA methylation. Consequently, lineage-associated genes (and LINE1) acquire a repressive epigenetic memory in pluripotent cells, which renders them incompetent for activation during future lineage-specification. Dppa2/4 thereby sculpt a permissive epigenome for development by targeting H3K4me3 to counteract de novo methylation during (re)programming; a function that has been co-opted by evolutionary young LINE1 to evade epigenetic decommissioning.
2020-05-28 | GSE151267 | GEO
Project description:N6-methyladenosine (m6A) is the most abundant internal modification on mammalian messenger RNA (mRNA). It is installed by a writer complex and can be reversed by erasers such as the fat mass and obesity-associated protein (FTO). Despite extensive research, the primary physiological substrates of FTO in mammalian tissues and development remain elusive. Here, we show that FTO mediates m6A demethylation of long-interspersed element-1 (LINE1) RNA in mouse embryonic stem cells (mESCs), regulating LINE1 RNA abundance and the local chromatin state, which in turn modulates transcription of LINE1-containing genes. FTO-mediated LINE1 RNA m6A demethylation also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development. Our results suggest broad effects of LINE1 RNA m6A demethylation by FTO in mammals.
2022-05-05 | GSE151780 | GEO
Project description:In mouse embryonic stem cells, the regulators of transposable elements are not well known. Here, we studied the proteins regulating mammalian-wide interspersed repeat (MIR), a short-interspersed nuclear elements (SINE) family using the CAPTURE2.0 system. We generated cell lines expressing biotinylated dCas9 protein and MIR-targeting sgRNAs, performed biotin pulldown to isolate MIR-associated proteins, and analyzed them using mass spectrometry.
2025-04-01 | PXD062330 | Pride
Project description:Deciphering the mechanisms that control the pluripotent ground state is key for understanding embryonic development. Nonetheless, the epigenetic regulation of ground-state mouse embryonic stem cells (mESCs) is not fully understood. Here, we identify the epigenetic protein MPP8 as being essential for ground-state pluripotency. Its depletion leads to cell cycle arrest and spontaneous differentiation. MPP8 has been suggested to repress LINE1 elements by recruiting the human silencing hub (HUSH) complex to H3K9me3-rich regions. Unexpectedly, we find that LINE1 elements are efficiently repressed by MPP8 lacking the chromodomain, while the unannotated C-terminus is essential for its function. Moreover, we show that SETDB1 recruits MPP8 to its genomic target loci, whereas transcriptional repression of LINE1 elements is maintained without retaining H3K9me3 levels. Taken together our findings demonstrate that MPP8 protects the DNA-hypomethylated pluripotent ground state through its association with the HUSH core complex, however, independently of detectable chromatin binding and maintenance of H3K9me3.
2021-03-21 | PXD019345 | Pride
Project description:The failure of treatment to deal with intractable cancer cells has raised the question of whether there is a special population of cells in tumor heterogeneity that exhibit resistant phenotypes that favor micrometastasis and have the potential to cause recurrence. One of the current points of view is that most solid cancers, including breast cancer, are stem cell diseases, and that these CSCs are critical to dissemination and metastasis. Our objective is to study the role of POU1F1 in breast cancer cell plasticity. Specifically, we will evaluate whether POU1F1 could modify the phenotype of normal -epithelial- cells to induce its transformation into CSCs/BCSCs
2025-05-06 | GSE287732 | GEO