Endogenous retroviruses act as enhancers to drive species-specific germline transcriptomes in mammals
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ABSTRACT:
PROVIDER: PRJNA596198 | ENA |
REPOSITORIES: ENA
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Project description:Gene regulation in the germline ensures the production of high-quality gametes, long-term maintenance of the species, and speciation. Germline transcriptomes undergo dynamic changes after the mitosis-to-meiosis transition in males and have been subject to evolutionary divergence among mammals. However, the mechanism that underlies germline regulatory divergence remains undetermined. Here, we show that endogenous retroviruses influence species-specific germline transcriptomes in mammals. We show that the endogenous retroviruses function as active enhancers to drive evolutionarily young (mouse or rodent specific) spermatogenesis-specific genes after the mitosis-to-meiosis transition in male mice. These ERV loci bear binding motifs for critical regulators of spermatogenesis such as A-MYB. The genome-wide transposition of ERVs might have rewired germline gene expression in a species-specific manner. Notably, these features are present in human spermatogenesis, but independently evolved ERVs are associated with expression of germline genes, demonstrating the prevalence of ERV-driven mechanisms in mammals. Together, we propose a model whereby species-specific transcriptomes are fine-tuned by endogenous retroviruses in the mammalian germline.
2020-05-28 | GSE142173 | GEO
Project description: Not available
| S-EPMC8246630 | biostudies-literature
Project description:Most endogenous retroviruses (ERVs) in mammals are incapable of retrotransposition; therefore, why ERV de-repression is associated with lethality during early development has been a mystery. Here we report that rapid and selective degradation of the TRIM28 heterochromatin adapter protein triggers dissociation of transcriptional condensates from loci encoding super-enhancer -driven pluripotency genes, and their association with transcribed ERV loci in murine embryonic stem cells. Knockdown of ERV RNAs or forced expression of super-enhancer -enriched transcription factors rescued condensate localization at super-enhancers in TRIM28-degraded cells. In a biochemical reconstitution system, ERV RNA facilitated partitioning of RNA Polymerase II, and the Mediator co- activator into phase-separated droplets. In TRIM28 knockout mouse embryos, single-cell RNA-Seq analysis revealed specific depletion of pluripotent lineages. We propose that coding and non-coding nascent RNAs, including those produced by retrotransposons, may facilitate “hijacking” of transcriptional condensates in various developmental and disease contexts.
2022-03-30 | GSE159468 | GEO
Project description:Prion-like spreading of protein misfolding is characteristic for neurodegenerative diseases, but the exact mechanisms of intercellular protein aggregate dissemination remain unresolved. Evidence accumulates that endogenous retroviruses, remnants of viral germline infections that are normally epigenetically silenced, become upregulated in neurodegenerative diseases such as amyotrophic lateral sclerosis and tauopathies. Here we uncover that activation of endogenous retroviruses affects prion-like spreading of proteopathic seeds. To identify changes in the proteome of donor cells that might contribute to protein aggregate spreading, we performed mass spectrometry analyses of total cell lysates and donor EV fractions using N2a cells expressing HA epitope-tagged Sup35 NM prion protein at early (P07) and late passages (P16) post cryopreservation. Among the proteins increased in donor cells and EVs upon prolonged culture, we identified mouse endogenous MLV retrovirus proteins to be highly increased.
2023-10-18 | PXD043201 | Pride
Project description:Here we show that in neural progenitor cells (NPCs) TRIM28 silences transcription of two groups of endogenous retroviruses (ERVs): IAP1 and MMERVK10C. Derepression of ERVs in Trim28-deficient NPCs was associated with a loss of H3K9me3 and resulted in transcriptional upregulation and reverse transcription. These findings demonstrate a unique dynamic transcriptional regulation of ERVs in NPCs. Analysis of upregulation of ERVs in Trim28-deficient NPCs
2015-01-07 | E-GEOD-45930 | biostudies-arrayexpress
Project description:We report DAXX-dependent deposition of histone H3.3 at at endogenous retroviruses in embryonic stem cells.
2015-07-16 | GSE70966 | GEO
Project description:Heterochromatin plays essential roles in repressing retrotransposons, e.g. endogenous retroviruses (ERVs) during mammalian development, but the contribution of retrotransposition to lethality observed in embryonic cells deficient for heterochromatin-mediated ERV repression is poorly understood. Here we report that selective degradation of the TRIM28 heterochromatin adapter protein leads to reduced association of transcriptional condensates with loci encoding super-enhancer -driven pluripotency genes in embryonic stem cells, a collapse of the pluripotency transcriptional circuit, and a pre-lethal restriction of pluripotent lineages in mouse embryos. De-repressed ERVs recruit transcriptional condensates in the absence of TRIM28, and ERV RNA facilitates condensation of RNA Polymerase II in vitro. We propose that retrotransposons contribute to the genomic distribution of nuclear condensates, and that RNA species may facilitate “hijacking” of transcriptional condensates in various developmental and disease contexts.
2022-07-08 | PXD021895 | Pride
Project description:Endogenous retroviruses (ERVs) and other transposons can act as tissue-specific regulators of gene expression in cis, with potential to affect biological processes. In cancer, epigenetic alterations and transcription factor misregulation may uncover the regulatory potential of typically repressed ERVs, which could contribute to tumour evolution and progression. Here, we asked whether transposons help to rewire oncogenic transcriptional circuits in acute myeloid leukaemia (AML). Using epigenomic data from both primary cells and cell lines, we have identified six ERV families that are frequently found in an open chromatin state in AML when compared to differentiated myeloid cells. A subset of these AML-associated ERVs harbour enhancer-specific histone modifications, and are bound by transcription factors that play key roles in haematopoiesis and in the pathogenesis of AML. Using CRISPR-mediated genetic and epigenetic editing, we have established causal links between ERV deregulation in AML and expression changes of adjacent genes. Finally, we show that deletion and epigenetic silencing of an ERV associated with the APOC1 gene leads to growth suppression by inducing apoptosis in leukemia cell lines. Our results suggest that ERV derepression provides an additional layer of gene regulation in AML that may be exploited by cancer cells to help drive oncogenic phenotypes.
2019-09-04 | GSE136763 | GEO
Project description:Endogenous retroviruses (ERVs) and other transposons can act as tissue-specific regulators of gene expression in cis, with potential to affect biological processes. In cancer, epigenetic alterations and transcription factor misregulation may uncover the regulatory potential of typically repressed ERVs, which could contribute to tumour evolution and progression. Here, we asked whether transposons help to rewire oncogenic transcriptional circuits in acute myeloid leukaemia (AML). Using epigenomic data from both primary cells and cell lines, we have identified six ERV families that are frequently found in an open chromatin state in AML when compared to differentiated myeloid cells. A subset of these AML-associated ERVs harbour enhancer-specific histone modifications, and are bound by transcription factors that play key roles in haematopoiesis and in the pathogenesis of AML. Using CRISPR-mediated genetic and epigenetic editing, we have established causal links between ERV deregulation in AML and expression changes of adjacent genes. Finally, we show that deletion and epigenetic silencing of an ERV associated with the APOC1 gene leads to growth suppression by inducing apoptosis in leukemia cell lines. Our results suggest that ERV derepression provides an additional layer of gene regulation in AML that may be exploited by cancer cells to help drive oncogenic phenotypes.
2019-09-04 | GSE136760 | GEO
Project description:Endogenous retroviruses (ERVs) and other transposons can act as tissue-specific regulators of gene expression in cis, with potential to affect biological processes. In cancer, epigenetic alterations and transcription factor misregulation may uncover the regulatory potential of typically repressed ERVs, which could contribute to tumour evolution and progression. Here, we asked whether transposons help to rewire oncogenic transcriptional circuits in acute myeloid leukaemia (AML). Using epigenomic data from both primary cells and cell lines, we have identified six ERV families that are frequently found in an open chromatin state in AML when compared to differentiated myeloid cells. A subset of these AML-associated ERVs harbour enhancer-specific histone modifications, and are bound by transcription factors that play key roles in haematopoiesis and in the pathogenesis of AML. Using CRISPR-mediated genetic and epigenetic editing, we have established causal links between ERV deregulation in AML and expression changes of adjacent genes. Finally, we show that deletion and epigenetic silencing of an ERV associated with the APOC1 gene leads to growth suppression by inducing apoptosis in leukemia cell lines. Our results suggest that ERV derepression provides an additional layer of gene regulation in AML that may be exploited by cancer cells to help drive oncogenic phenotypes.
2019-09-04 | GSE136759 | GEO