title: DNA methylation restrains transposons from adopting a chromatin signature permissive for meiotic recombination.
abstract: DNA methylation is essential for protecting the mammalian germline against transposons. When DNA methylation-based transposon control is defective, meiotic chromosome pairing is consistently impaired during spermatogenesis: How and why meiosis is vulnerable to transposon activity is unknown. Using two DNA methylation-deficient backgrounds, the Dnmt3L and Miwi2 mutant mice, we reveal that DNA methylation is largely dispensable for silencing transposons before meiosis onset. After this, it becomes crucial to back up to a developmentally programmed H3K9me2 loss. Massive retrotransposition does not occur following transposon derepression, but the meiotic chromatin landscape is profoundly affected. Indeed, H3K4me3 marks gained over transcriptionally active transposons correlate with formation of SPO11-dependent double-strand breaks and recruitment of the DMC1 repair enzyme in Dnmt3L(-/-) meiotic cells, whereas these features are normally exclusive to meiotic recombination hot spots. Here, we demonstrate that DNA methylation restrains transposons from adopting chromatin characteristics amenable to meiotic recombination, which we propose prevents the occurrence of erratic chromosomal events.
authors.affiliation: UMR3215, CNRS, Paris 75005, France; U934, INSERM Institut Curie, Paris 75005, France;
authors.forename: Natasha
authors.initials: N
authors.lastname: Zamudio
authors.affiliation: UMR3215, CNRS, Paris 75005, France; U934, INSERM Institut Curie, Paris 75005, France;
authors.forename: Joan
authors.initials: J
authors.lastname: Barau
authors.affiliation: UMR3215, CNRS, Paris 75005, France; U934, INSERM Institut Curie, Paris 75005, France; U900, INSERM, Paris 75005, France; Mines ParisTech, Institut Curie, Paris 75005, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Teissandier
authors.affiliation: UMR3215, CNRS, Paris 75005, France; U934, INSERM Institut Curie, Paris 75005, France;
authors.forename: Marius
authors.initials: M
authors.lastname: Walter
authors.affiliation: UMR3215, CNRS, Paris 75005, France; U934, INSERM Institut Curie, Paris 75005, France;
authors.forename: Maté
authors.initials: M
authors.lastname: Borsos
authors.affiliation: U900, INSERM, Paris 75005, France; Mines ParisTech, Institut Curie, Paris 75005, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Servant
authors.affiliation: UMR3215, CNRS, Paris 75005, France; U934, INSERM Institut Curie, Paris 75005, France;
authors.forename: Déborah
authors.initials: D
authors.lastname: Bourc'his
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation; D004251:DNA Transposable Elements / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics; D006657:Histones / Q000235:genetics / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D009154:Mutation; D011995:Recombination, Genetic / Q000235:genetics*; D013091:Spermatogenesis / Q000235:genetics
chemical_list: D060565:Argonaute Proteins; D002843:Chromatin; D004251:DNA Transposable Elements; D006657:Histones; C546575:PIWIL4 protein, mouse; C498796:Dnmt3l protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: DNA methylation; chromatin; fertility; germ cells; meiosis; transposons