An endosiRNA-Based Repression Mechanism Counteracts Transposon Activation during Global DNA Demethylation in Embryonic Stem Cells

Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESC...

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Vydáno v:Cell stem cell Ročník 21; číslo 5; s. 694
Hlavní autoři: Berrens, Rebecca V, Andrews, Simon, Spensberger, Dominik, Santos, Fátima, Dean, Wendy, Gould, Poppy, Sharif, Jafar, Olova, Nelly, Chandra, Tamir, Koseki, Haruhiko, von Meyenn, Ferdinand, Reik, Wolf
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 02.11.2017
Témata:
germ line
repeats
DNMT1
RNAi
IAP elements
endogenous retroviruses
transposable element
primordial germ cell
small RNAs
ISSN:1875-9777, 1875-9777
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Shrnutí:Erasure of DNA methylation and repressive chromatin marks in the mammalian germline leads to risk of transcriptional activation of transposable elements (TEs). Here, we used mouse embryonic stem cells (ESCs) to identify an endosiRNA-based mechanism involved in suppression of TE transcription. In ESCs with DNA demethylation induced by acute deletion of Dnmt1, we saw an increase in sense transcription at TEs, resulting in an abundance of sense/antisense transcripts leading to high levels of ARGONAUTE2 (AGO2)-bound small RNAs. Inhibition of Dicer or Ago2 expression revealed that small RNAs are involved in an immediate response to demethylation-induced transposon activation, while the deposition of repressive histone marks follows as a chronic response. In vivo, we also found TE-specific endosiRNAs present during primordial germ cell development. Our results suggest that antisense TE transcription is a "trap" that elicits an endosiRNA response to restrain acute transposon activity during epigenetic reprogramming in the mammalian germline.
Bibliografie:ObjectType-Article-1
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ISSN:1875-9777
1875-9777
DOI:10.1016/j.stem.2017.10.004