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

AI Article Synopsis

  • Proper meiosis and fertility in mice and humans rely on programmed DNA double-strand breaks (DSBs), regulated by the protein PRDM9, which has both DNA-binding and methyltransferase activities.
  • PRDM9 specifically influences the deposition of histone methylation marks (H3K4me3 and H3K36me3) required for establishing DSBs at its binding sites.
  • Analysis of mice with different PRDM9 variants shows that each variant independently creates unique H3K4me3 marks, highlighting a complex mechanism for determining DSB sites through PRDM9 binding and histone modification.

Article 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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Source
http://dx.doi.org/10.1016/j.molcel.2018.01.033DOI Listing

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