Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA397755 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5920630.fastq.gz | Fastqsanger.gz | |||
| SRR5920631.fastq.gz | Fastqsanger.gz | |||
| SRR5920632.fastq.gz | Fastqsanger.gz | |||
| SRR5920633.fastq.gz | Fastqsanger.gz | |||
| SRR5920634.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
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Project description:DNA methylation and other repressive epigenetic marks are erased genome-wide in mammalian primordial germ cells (PGCs), the early embryo and in naïve embryonic stem cells (ESCs). This is a critical phase for transposon element (TE) defense since presumably alternative pathways need to be employed to limit their activity. It has been reported that pervasive transcription is enriched for TEs in ESCs in comparison to somatic cells. Here we test the hypothesis that pervasive transcription overlapping TEs forms a sensor for loss of their transcriptional repression. Overlapping sense and antisense transcription is found in TEs, and the increase of sense transcription induced by acute deletion of DNMT1 leads to the emergence of small RNAs. These small RNAs are loaded into ARGONAUTE 2 suggesting an endosiRNA mechanism for transposon silencing. Indeed, deletion of DICER reveals this mechanism to be important for silencing of certain transposon classes, while others are additionally repressed by deposition of repressive histone marks. Our observations suggest that pervasive transcription overlapping with TEs resulting in endosiRNAs is a transposon sensor that restrains their activity during epigenetic reprogramming in the germline.
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Project description:DNA methylation and other repressive epigenetic marks are erased in the mammalian germline and transposable elements (TEs) acquire the potential to be transcribed. This is a critical phase for genome defense and complementary TE silencing pathways are required to limit their activity. We find overlapping sense/antisense transcription in TEs in mouse embryonic stem cells, with an increase of sense transcription induced by acute deletion of Dnmt1, leading to increased abundance of small RNAs. These small RNAs are loaded into ARGONAUTE2 (AGO2) suggesting an endosiRNA based silencing mechanism. Reduction of Dicer and Ago2 levels reveals that small RNAs are involved in an immediate response to transposon activation by demethylation, while the deposition of repressive histone marks represents an ensuing chronic response. Dicer dependent endosiRNAs which map to TEs are also found in vivo during primordial germ cell development. Our results suggest that TE antisense transcription acts as a trap that restrains acute transposon activity through small RNAs during epigenetic reprogramming in the germline.
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