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Elife. 2016 Jan 27;5. pii: e11418. doi: 10.7554/eLife.11418.

An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells.

Walter M1,2,3,4, Teissandier A1,3,4,2,5,6,7, Pérez-Palacios R1,3,4,2, Bourc'his D1,3,4,2.

Author information

1
Department of Genetics and Developmental Biology, Institut Curie, Paris, France.
2
Paris Science Lettres Research University, .
3
UMR3215, CNRS, Paris, France.
4
U934, Inserm, Paris, France.
5
Bioinformatics, Biostatistics, Epidemiology and Computational Systems Biology of Cancer, Institut Curie, Paris, France.
6
Mines Paris Tech, Paris, France.
7
U900, Inserm, Paris, France.

Abstract

DNA methylation is extensively remodeled during mammalian gametogenesis and embryogenesis. Most transposons become hypomethylated, raising the question of their regulation in the absence of DNA methylation. To reproduce a rapid and extensive demethylation, we subjected mouse ES cells to chemically defined hypomethylating culture conditions. Surprisingly, we observed two phases of transposon regulation. After an initial burst of de-repression, various transposon families were efficiently re-silenced. This was accompanied by a reconfiguration of the repressive chromatin landscape: while H3K9me3 was stable, H3K9me2 globally disappeared and H3K27me3 accumulated at transposons. Interestingly, we observed that H3K9me3 and H3K27me3 occupy different transposon families or different territories within the same family, defining three functional categories of adaptive chromatin responses to DNA methylation loss. Our work highlights that H3K9me3 and, most importantly, polycomb-mediated H3K27me3 chromatin pathways can secure the control of a large spectrum of transposons in periods of intense DNA methylation change, ensuring longstanding genome stability.

KEYWORDS:

DNA methylation; chromatin; chromosomes; developmental biology; genes; mouse; stem cells; transposons

PMID:
26814573
PMCID:
PMC4769179
DOI:
10.7554/eLife.11418
[Indexed for MEDLINE]
Free PMC Article

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