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The COMPASS Subunit Spp1 Links Histone Methylation to Initiation of Meiotic Recombination

Science  11 Jan 2013:
Vol. 339, Issue 6116, pp. 215-218
DOI: 10.1126/science.1225739

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Repair and Recombination

In most sexually reproducing organisms, the haploid gametes are produced by meiosis, a specialized cell-division during which recombination between the parental chromosomes ensures proper chromosome segregation. Double-strand breaks (DSB) generated in the DNA drive this recombination and are linked to recombination hotspots in the chromatin where histone H3 is methylated on lysine residue 4 (H3K4me) by the Set1C/COMPASS enzyme complex. Acquaviva et al. (p. 215, published online 15 November) show that the Mer2/Mei4/Rec114 complex of the DSB generating machinery is linked to the Set1C/COMPASS enzyme complex through the Spp1 subunit, which contains a PHD-finger capable of binding to H3K4me. The Spp1 subunit recruits the Mer2 protein to sites where recombination will occur, probably by binding to both the H3K4me-marked chromatin and other factors.

Abstract

During meiosis, combinatorial associations of genetic traits arise from homologous recombination between parental chromosomes. Histone H3 lysine 4 trimethylation marks meiotic recombination hotspots in yeast and mammals, but how this ubiquitous chromatin modification relates to the initiation of double-strand breaks (DSBs) dependent on Spo11 remains unknown. Here, we show that the tethering of a PHD-containing protein, Spp1 (a component of the COMPASS complex), to recombinationally cold regions is sufficient to induce DSB formation. Furthermore, we found that Spp1 physically interacts with Mer2, a key protein of the differentiated chromosomal axis required for DSB formation. Thus, by interacting with H3K4me3 and Mer2, Spp1 promotes recruitment of potential meiotic DSB sites to the chromosomal axis, allowing Spo11 cleavage at nearby nucleosome-depleted regions.

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