Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Stem Cell Activity-Coupled Suppression of Endogenous Retrovirus Governs Adult Tissue Regeneration [RNA-seq]

ABSTRACT: Mammalian retrotransposons constitute 40% of the genome. During tissue regeneration, adult stem cells coordinately repress retrotransposons and activate lineage genes, but how this coordination is controlled is poorly understood. Here, we observed that dynamic expression of histone methyltransferase SETDB1 (a retrotransposon repressor) closely mirrors stem cell activities in the murine skin. SETDB1 ablation leads to reactivation of endogenous retroviruses (ERVs, a type of retrotransposon) and assembly of viral-like particles, resulting in hair loss and stem cell exhaustion that is reversible by antiviral drugs. Mechanistically, at least two molecularly and spatially distinct pathways are responsible: antiviral defense mediated by hair follicle stem cells and progenitors, and antiviral independent response due to replication stress in transient amplifying cells. ERV reactivation is promoted by DNA demethylase TET-mediated hydroxymethylation and recapitulated by ablating cell fate transcription factors. Together, we demonstrated ERV silencing is coupled with stem cell activity and essential for adult hair regeneration.

ORGANISM(S): Mus musculus

PROVIDER: GSE226579 | GEO | 2024/10/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Stem Cell Activity-Coupled Suppression of Endogenous Retrovirus Governs Adult Tissue Regeneration

Project description:Mammalian retrotransposons constitute 40% of the genome. During tissue regeneration, adult stem cells coordinately repress retrotransposons and activate lineage genes, but how this coordination is controlled is poorly understood. Here, we observed that dynamic expression of histone methyltransferase SETDB1 (a retrotransposon repressor) closely mirrors stem cell activities in the murine skin. SETDB1 ablation leads to reactivation of endogenous retroviruses (ERVs, a type of retrotransposon) and assembly of viral-like particles, resulting in hair loss and stem cell exhaustion that is reversible by antiviral drugs. Mechanistically, at least two molecularly and spatially distinct pathways are responsible: antiviral defense mediated by hair follicle stem cells and progenitors, and antiviral independent response due to replication stress in transient amplifying cells. ERV reactivation is promoted by DNA demethylase TET-mediated hydroxymethylation and recapitulated by ablating cell fate transcription factors. Together, we demonstrated ERV silencing is coupled with stem cell activity and essential for adult hair regeneration.

2024-10-17 | GSE226580 | GEO

Stem Cell Activity-Coupled Suppression of Endogenous Retrovirus Governs Adult Tissue Regeneration [scRNA-seq]

2024-10-17 | GSE233240 | GEO

Stem Cell Activity-Coupled Suppression of Endogenous Retrovirus Governs Adult Tissue Regeneration [WGBS]

2024-10-17 | GSE227078 | GEO

Stem Cell Activity-Coupled Suppression of Endogenous Retrovirus Governs Adult Tissue Regeneration [ChIP-seq/hMeDIP]

2024-10-17 | GSE226578 | GEO

Stem Cell Activity-Coupled Suppression of Endogenous Retrovirus Governs Adult Tissue Regeneration [ATAC-seq]

2024-10-17 | GSE226577 | GEO

Setdb1 is required for persistence of H3K9me3 and repression of endogenous retroviruses in mouse primordial germ cells

Project description:Transcription of endogenous retroviruses (ERVs) is inhibited by de novo DNA methylation during gametogenesis, a process initiated after birth in oocytes and at ~E15.5 in prospermatogonia. Earlier in germline development however, the genome, including most retrotransposons, is progressively demethylated, with young ERVK and ERV1 elements retaining 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 method. Although these repressive histone modifications are predominantly found on distinct genomic regions in E13.5 PGCs, they concurrently mark partially methylated LTRs and LINE1 elements. Germline-specific conditional knock-out (KO) of the H3K9 methyltransferase SETDB1 yields a decrease of both histone marks and DNA methylation at H3K9me3 enriched retrotransposon families. Strikingly, Setdb1-KO E13.5 PGCs show concomitant de-repression of many marked ERVs, including 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 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. H3K9me3, H3K27me3 and expression profiles in Setdb1 WT, Het and KO male and female E13.5 PGCs.

2014-09-01 | E-GEOD-60377 | biostudies-arrayexpress

LTR-retrotransposon control by tRNA-derived small RNA

Project description:Transposon reactivation is an inherent danger in cells that lose epigenetic silencing during developmental reprogramming. In the mouse, LTR-retrotransposons, or endogenous retroviruses (ERV), account for most novel insertions and are expressed in the absence of histone H3 Lysine 9 trimethylation in preimplantation stem cells. We found abundant, 18 nt tRNA-derived small RNA (tRF) in these cells, and ubiquitously expressed 22 nt tRFs, that include the 3' terminal CCA of mature tRNAs, and target the tRNA primer binding site (PBS) essential for ERV reverse transcription. We show that the two most active ERV families, IAP and MusD/ETn, are major targets and are strongly inhibited by tRFs in retrotransposition assays. 22 nt tRFs post-transcriptionally silence coding-competent ERVs, while 18 nt tRFs specifically interfere with reverse transcription and retrotransposon mobility. The PBS offers a unique target to specifically inhibit LTR-retrotransposons and tRF-targeting is a potentially highly conserved mechanism of small RNA-mediated transposon control.

2017-06-29 | GSE82199 | GEO

Retrotransposon derepression leads to activation of the unfolded protein response and apoptosis in pro B cells

Project description:The establishment of distinct transcription programs during development is controlled by transcription factor networks acting in specific chromatin environments. The H3K9me3-specific histone methyltransferase Setdb1 impacts on transcriptional regulation by repressing both developmental genes and retrotransposons. How impaired retrotransposon silencing may lead to developmental phenotypes is currently unclear. Here we show that loss of Setdb1 in pro-B cells completely abrogates B cell development. In pro-B cells, Setdb1 is dispensable for silencing of lineage-inappropriate developmental genes. Instead, we detect strong derepression of endogenous Murine Leukemia Virus (MLV) copies. Production of MLV proteins leads to activation of the unfolded protein response pathway and apoptosis. Thus, our data demonstrate that B cell development critically depends on the proper repression of retrotransposon sequences through Setdb1. Transcriptomic and chromatin analysis of control and Setdb1-deficient pro-B cells

2016-07-20 | E-GEOD-77636 | biostudies-arrayexpress

The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity

Project description:The RNA modification N6-methyladenosine (m6A) has critical roles in many biological processes. However, the function of m6A in the early phase of mammalian development remains poorly understood. Here we show that the m6A reader YT521-B homology-domain-containing protein 1 (YTHDC1) is required for the maintenance of mouse embryonic stem (ES) cells in an m6A-dependent manner, and that its deletion initiates cellular reprogramming to a 2C-like state. Mechanistically, YTHDC1 binds to the transcripts of retrotransposons (such as intracisternal A particles, ERVK and LINE1) in mouse ES cells and its depletion results in the reactivation of these silenced retrotransposons, accompanied by a global decrease in SETDB1-mediated trimethylation at lysine 9 of histone H3 (H3K9me3). We further demonstrate that YTHDC1 and its target m6A RNAs act upstream of SETDB1 to repress retrotransposons and Dux, the master inducer of the two-cell stage (2C)-like program. This study reveals an essential role for m6A RNA and YTHDC1 in chromatin modification and retrotransposon repression. This SuperSeries is composed of the SubSeries listed below.

2021-01-24 | GSE146467 | GEO

Setdb1 is required for persistence of H3K9me3 and repression of endogenous retroviruses in mouse primordial germ cells

2014-09-01 | GSE60377 | GEO