| First Author | Diagouraga B | Year | 2018 |
| Journal | Mol Cell | Volume | 69 |
| Issue | 5 | Pages | 853-865.e6 |
| PubMed ID | 29478809 | Mgi Jnum | J:255344 |
| Mgi Id | MGI:6114980 | Doi | 10.1016/j.molcel.2018.01.033 |
| Citation | Diagouraga B, et al. (2018) PRDM9 Methyltransferase Activity Is Essential for Meiotic DNA Double-Strand Break Formation at Its Binding Sites. Mol Cell 69(5):853-865.e6 |
| abstractText | 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. |
