Pluto Bioinformatics

GSE102446: Pervasive transcription and endosiRNAs restrain transposons during global demethylation in embryonic stem cells [RNA-Seq 2]

Bulk RNA sequencing

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. SOURCE: Felix Krueger ( - The Babraham Institute

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