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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Bibliographic Details
Published in:Cell stem cell Vol. 21; no. 5; p. 694
Main Authors: 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
Format: Journal Article
Language:English
Published: United States 02.11.2017
Subjects:
germ line
repeats
DNMT1
RNAi
IAP elements
endogenous retroviruses
transposable element
primordial germ cell
small RNAs
ISSN:1875-9777, 1875-9777
Online Access:Get more information
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Summary: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.
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ISSN:1875-9777
1875-9777
DOI:10.1016/j.stem.2017.10.004