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PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites

Abstract : The programmed formation of hundreds of DNA double-strand breaks (DSBs) is essential for proper meiosis and fertility. In mice and humans, the location of these breaks is determined by the meiosis-specific protein PRDM9, through the DNA-binding specificity of its zinc-finger domain. PRDM9 also has methyltransferase activity. Here, we show that this activity is required for H3K4me3 and H3K36me3 deposition and for DSB formation at PRDM9-binding sites. By analyzing mice that express two PRDM9 variants with distinct DNA-binding specificities, we show that each variant generates its own set of H3K4me3 marks independently from the other variant. Altogether, we reveal several basic principles of PRDM9-dependent DSB site determination, in which an excess of sites are designated through PRDM9 binding and subsequent histone methylation, from which a subset is selected for DSB formation.
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https://hal.archives-ouvertes.fr/hal-01730632
Contributor : Catherine Larose <>
Submitted on : Tuesday, March 13, 2018 - 2:28:20 PM
Last modification on : Wednesday, September 15, 2021 - 11:26:04 AM

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Boubou Diagouraga, Julie Clément, L. Duret, Jan Kadlec, Bernard de Massy, et al.. PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites. Molecular Cell, Elsevier, 2018, 69 (5), pp.853 - 865.e6. ⟨10.1016/j.molcel.2018.01.033⟩. ⟨hal-01730632⟩

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