BioProject

Meiotic DSB, catalyzed by the Spo11 transesterase protein and accessory DSB proteins, form in the nucleosome depleted regions (NDR) at promoters, preferentially those located on the chromosome loops that shape meiotic chromosomes, whereas the DSB proteins are located on chromosome axes at the basis of these loops. More...

Meiotic DSB, catalyzed by the Spo11 transesterase protein and accessory DSB proteins, form in the nucleosome depleted regions (NDR) at promoters, preferentially those located on the chromosome loops that shape meiotic chromosomes, whereas the DSB proteins are located on chromosome axes at the basis of these loops. Mechanisms bridging these two chromosomal regions for DSB formation have remained elusive. Here we show that Spp1, a conserved member of the histone H3K4 methyltransferase Set1 complex, is required for normal levels of DSB formation and is associated with chromosome axes in the DSB-rich domains during meiosis. Moreover, Spp1 physically interacts with the Mer2 axis-associated DSB protein, and uses its PHD finger as a magnet to read H3K4 trimethylation close to promoters, tether these regions to chromosome axes and activate cleavage in the nearby promoter by the DSB proteins. We further show that in the absence of Spp1 or the Set1 complex, DSB are introduced at a few new sites, located in promoters of transcriptionally induced genes, suggesting another selection mechanism of preferred DSB sequences. This paper provides the molecular mechanism linking H3K4me3 to the DSB forming machinery, by the meiosis-specific specialization of Spp1 as an active member of the DSB complex and a reader of H3K4me3, and opens perspectives for the study of DSB formation at mammalian recombination hotspots that are also enriched in H3K4me3. Overall design: ChIP-chip experiment in vegetative or meiotic diploid SK1 yeast cells - two biological replicates Less...