Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Co-option of endogenous retroviruses through genetic escape from TRIM28 repression

ABSTRACT: Endogenous retroviruses (ERVs) have rewired host gene networks. To explore the origins of co-option, we employed an active murine ERV, IAPEz, and an embryonic stem cell (ESC) to neural progenitor cell (NPC) differentiation model. Epigenetic silencing via TRIM28 maps to a 190bp sequence encoding the IAP signal peptide, which confers retrotransposition activity. A subset of ‘escapee’ IAPs (~15%) exhibit significant genetic divergence from this sequence. Canonical repressed IAPs succumb to a previously undocumented demarcation by H3K9me3 and H3K27me3 in NPCs. Escapee IAPs, in contrast, evade epigenetic repression in both cell types, resulting in their transcriptional derepression, particularly in NPCs. We validate the enhancer function of a 47bp sequence within the U3 region of the LTR and show that escapee IAPs convey an activating effect on nearby neural genes. In sum, co-opted ERVs stem from genetic escapees that have lost vital sequences required for both TRIM28 restriction and autonomous retrotransposition.

ORGANISM(S): Mus musculus

PROVIDER: GSE207184 | GEO | 2023/05/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

TRIM28 silences endogenous retroviruses in neural progenitor cells

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

TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells

Project description:TRIM28 (KAP1 - KRAB-associated protein 1) is critical for the silencing of endogenous retroviruses (ERVs) in embryonic stem (ES) cells. Here, we reveal that an essential impact of this process is the protection of cellular gene expression in early embryos from perturbation by cis-acting activators contained within these genetic invaders. In TRIM28-depleted ES cells, repressive chromatin marks at ERVs are replaced by histone modifications typical of active enhancers, stimulating transcription of nearby cellular genes, notably those harboring bivalent promoters. Correspondingly, ERV-derived sequences can repress or enhance expression from an adjacent promoter in transgenic embryos depending on their TRIM28-sensitivity in ES cells. TRIM28-mediated control of ERVs is therefore crucial not just to prevent retrotransposition, but more broadly to safeguard the transcriptional dynamics of early embryos. Analyses of transcriptional profiles and chromatin state in TRIM28 WT and KO cells

2012-12-04 | E-GEOD-41903 | biostudies-arrayexpress

TRIM28 silences endogenous retroviruses in neural progenitor cells

2015-01-07 | GSE45930 | GEO

Hijacking of transcriptional condensates by endogenous retroviruses

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

TRIM28 repression of retrotransposon-based enhancers is necessary to preserve transcriptional dynamics in embryonic stem cells

2012-12-04 | GSE41903 | GEO

Activation of endogenous retroviruses during brain development causes neuroinflammation

Project description:Endogenous retroviruses (ERVs) make up a large fraction of mammalian genome and are thought to contribute to human disease, including brain disorders. Aberrant activation of ERVs constitute a potential trigger for neuroinflammation, but mechanistic insight into this phenomenon remains unclear. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons. In vivo disruption of Trim28 in cortical NPCs during brain development resulted in viable offspring expressing high levels of ERVs in excitatory neurons in the adult brain of mice. Neuronal ERV expression was linked to inflammation, including activated microglia, and aggregates of ERV-derived proteins. This study demonstrates that brain development is a critical period for the silencing of ERVs and provides causal in vivo evidence demonstrating that transcriptional activation of ERV in neurons results in neuroinflammation.

2021-02-24 | GSE154196 | GEO

RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs (MeRIP-Seq)

Project description:N6-methyladenosine (m6A) methyltransferase METTL3 mainly mediates mRNA m6A methylation and plays important roles in various biological processes. Here we report a chromatin-based role for METTL3 in heterochromatin integrity regulation in mouse embryonic stem cells (mESCs). We show that in mESCs METTL3 predominantly localizes to one of the most active endogenous retroviruses (ERVs) families, the intracisternal A-type particles (IAPs). We further show that METTL3 knockout (KO) impairs deposition of multiple heterochromatin marks on METTL3-targeted IAPs, and upregulates IAP transcription without affecting the stability of the resulting RNAs. De-repression can be rescued by wildtype but not catalytically inactive METTL3, suggesting that METTL3-mediated methylation is important for heterochromatin silencing. Mechanistically, we demonstrate that METTL3 physically interacts with the H3K9 tri-methyltransferase SETDB1 and its regulator TRIM28, and reciprocally promote each other’s localization to IAPs. Importantly, we show that m6A catalytical activity of METTL3 is necessary for its own recruitment to chromatin but not its interactions with SETDB1 and TRIM28. Taken together, our findings demonstrate that RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs.

2020-12-09 | GSE154138 | GEO

RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs [YTHDC1_ChIP]

2020-12-09 | GSE145135 | GEO

RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs [YTHDC1_ChIRP-Seq]

2020-12-09 | GSE145134 | GEO

RNA m6A modification mediated by METTL3 is important for IAP heterochromatin integrity in mESCs (total RNA-Seq 2)

2020-12-09 | GSE154139 | GEO