Meiotic recombination cold spots in chromosomal cohesion sites
Meiotic recombination cold spots in chromosomal cohesion sites
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DOI：
10.1111/gtc.12138
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发表时间：
2014-05
期刊：
影响因子：
2.1
通讯作者：
Masaru Ito;Kazuto Kugou;Jeffrey A. Fawcett;S. Mura;S. Ikeda;H. Innan;K. Ohta
中科院分区：
文献类型：
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作者：
Masaru Ito;Kazuto Kugou;Jeffrey A. Fawcett;S. Mura;S. Ikeda;H. Innan;K. Ohta
被称为轴环结构的减数分裂染色体结构和组蛋白修饰已被证明调节依赖于Spo11的DNA双链断裂(DSB)的形成，从而触发减数分裂重组。利用全基因组染色质免疫沉淀(CHIP)分析和深度测序，我们比较了轴蛋白Rec8(减数分裂粘附素的Kleisin亚基)和共价结合到Spo11的寡聚DNA的全基因组分布，表明了DSB位点。在Rec8结合位点之间，DSB位点的频率总体上是恒定的。然而，在Rec8结合位点周围±0.8kb的区域观察到DSB冷点。与轴相关的冷点并不是由于Spo11的定位被排除在轴上，因为芯片实验表明，在DSB形成过程中，大量的Spo11持续存在于Rec8结合位点。与其他区域不同，Spo11与Gal4DNA结合域(Gal4BD-Spo11)紧密结合在REC8结合部位附近(≤0.8kb)，很难形成减数分裂DSB。此外，在Rec8结合部位，H3K4三甲基化(H3K4me3)显著减少。这些结果表明，组蛋白H3K4me3的减少与轴上Spo11活性的失活相结合，阻止了DSB热点的形成。
Meiotic chromosome architecture called ‘axis–loop structures’ and histone modifications have been shown to regulate the Spo11‐dependent formation of DNA double‐strand breaks (DSBs) that trigger meiotic recombination. Using genome‐wide chromatin immunoprecipitation (ChIP) analyses followed by deep sequencing, we compared the genome‐wide distribution of the axis protein Rec8 (the kleisin subunit of meiotic cohesin) with that of oligomeric DNA covalently bound to Spo11, indicative of DSB sites. The frequency of DSB sites is overall constant between Rec8 binding sites. However, DSB cold spots are observed in regions spanning ±0.8 kb around Rec8 binding sites. The axis‐associated cold spots are not due to the exclusion of Spo11 localization from the axis, because ChIP experiments showed that substantial Spo11 persists at Rec8 binding sites during DSB formation. Spo11 fused with Gal4 DNA binding domain (Gal4BD‐Spo11) tethered in close proximity (≤0.8 kb) to Rec8 binding sites hardly forms meiotic DSBs, in contrast with other regions. In addition, H3K4 trimethylation (H3K4me3) remarkably decreases at Rec8 binding sites. These results suggest that reduced histone H3K4me3 in combination with inactivation of Spo11 activity on the axis discourages DSB hot spot formation.