Spp1, a Member of the Set1 Complex, Promotes Meiotic DSB Formation in Promoters by Tethering Histone H3K4 Methylation Sites to Chromosome Axes

SummaryMeiotic chromosomes are organized into arrays of loops that are anchored to the chromosome axis structure. Programmed DNA double-strand breaks (DSBs) that initiate meiotic recombination, catalyzed by Spo11 and accessory DSB proteins, form in loop sequences in promoters, whereas the DSB proteins are located on chromosome axes. 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 during meiosis, where it physically interacts with the Mer2 DSB protein. The PHD finger module of Spp1, which reads H3K4 methylation close to promoters, promotes DSB formation by tethering these regions to chromosome axes and activating cleavage by the DSB proteins. This paper provides the molecular mechanism linking DSB sequences to chromosome axes and explains why H3K4 methylation is important for meiotic recombination.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (115 K)Download as PowerPoint slideHighlights► Spp1 and histone H3K4 residue are important for meiotic DSB formation ► Spp1 physically interacts with the DSB protein Mer2 ► Spp1 in meiosis is not with RNA Pol II, but on chromosome axes in DSB-rich domains ► Spp1’s PHD finger tethers H3K4me3 regions to chromosome axes for DSB formation