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

被引:152
作者
Acquaviva, Laurent [1 ]
Szekvoelgyi, Lorant [2 ,4 ]
Dichtl, Bernhard [3 ]
Dichtl, Beatriz Solange [3 ]
Saint Andre, Christophe de La Roche [1 ]
Nicolas, Alain [2 ]
Geli, Vincent [1 ]
机构
[1] Aix Marseille Univ, Inst Paoli Calmettes, Marseille Canc Res Ctr CRCM, INSERM,CNRS,U1068,UMR7258, F-13009 Marseille, France
[2] Univ Paris 06, CNRS, Inst Curie, Ctr Rech,UMR3244, F-75248 Paris, France
[3] Deakin Univ, Sch Life & Environm Sci, Ctr Cellular & Mol Biol, Melbourne, Vic 3125, Australia
[4] Univ Debrecen, Med & Hlth Sci Ctr, Dept Biophys & Cell Biol, H-4012 Debrecen, Hungary
基金
瑞士国家科学基金会;
关键词
STRAND BREAK FORMATION; H3; TRIMETHYLATION; GENE-EXPRESSION; SITES; PROMOTER; FEATURES; HOTSPOTS; COMPLEX; PRDM9; ONSET;
D O I
10.1126/science.1225739
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:215 / 218
页数:4
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