PRDM9 binding organizes hotspot nucleosomes and limits Holliday junction migration.
PRDM9 binding organizes hotspot nucleosomes and limits Holliday junction migration.
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DOI：
10.1101/gr.170167.113
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发表时间：
2014-05
期刊：
影响因子：
7
通讯作者：
Paigen K
中科院分区：
文献类型：
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作者：
Baker CL;Walker M;Kajita S;Petkov PM;Paigen K
在哺乳动物中，减数分裂期间的基因重组仅限于一组称为热点的1至2 kb区域。它们的位置主要由锌指蛋白PRDM9决定，该蛋白与热点地区的DNA结合，随后使用其SET结构域局部三甲基化赖氨酸4处的组蛋白H3 （H3K4me3）。这为双链断裂（DSB）的形成和染色单体之间DNA的相互交换奠定了基础，形成了霍利迪结。在这里，我们报告了使用两种仅在PRDM9锌指结构域不同的近交小鼠品系对PRDM9依赖性组蛋白修饰的全基因组分析。我们发现PRDM9结合积极地将核小体重组成对称的模式，创造了一个扩展的核小体耗尽区域。这些区域以一个一致的PRDM9结合基序为中心，其位置和身份在体外得到了证实。我们还发现dsb集中在核小体缺失区域内的PRDM9结合基序上。将这些结果与遗传杂交数据相结合，我们发现杂交仅限于H3K4me3标记的区域。我们认为，prdm9修饰的核小体创造了一个允许的环境，首先指导dsb的位置，然后定义Holliday结分支迁移的边界。
In mammals, genetic recombination during meiosis is limited to a set of 1- to 2-kb regions termed hotspots. Their locations are predominantly determined by the zinc finger protein PRDM9, which binds to DNA in hotspots and subsequently uses its SET domain to locally trimethylate histone H3 at lysine 4 (H3K4me3). This sets the stage for double-strand break (DSB) formation and reciprocal exchange of DNA between chromatids, forming Holliday junctions. Here we report genome-wide analyses of PRDM9-dependent histone modifications using two inbred mouse strains differing only in their PRDM9 zinc finger domain. We show that PRDM9 binding actively reorganizes nucleosomes into a symmetrical pattern, creating an extended nucleosome-depleted region. These regions are centered by a consensus PRDM9 binding motif, whose location and identity was confirmed in vitro. We also show that DSBs are centered over the PRDM9 binding motif within the nucleosome-depleted region. Combining these results with data from genetic crosses, we find that crossing-over is restricted to the region marked by H3K4me3. We suggest that PRDM9-modified nucleosomes create a permissible environment that first directs the location of DSBs and then defines the boundaries of Holliday junction branch migration.
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DOI：
10.1093/dnares/dst059
发表时间：
2014-06
期刊：
DNA research : an international journal for rapid publication of reports on genes and genomes
影响因子：
--
作者：
Kono H;Tamura M;Osada N;Suzuki H;Abe K;Moriwaki K;Ohta K;Shiroishi T
通讯作者：
Shiroishi T
影响因子：
10.5
作者：
Cole, Francesca;Keeney, Scott;Jasin, Maria
通讯作者：
Jasin, Maria
影响因子：
12.3
作者：
Billings, Timothy;Parvanov, Emil D.;Petkov, Petko M.
通讯作者：
Petkov, Petko M.
模因套件：用于发现和搜索的工具。
影响因子：
14.9
作者：
Bailey TL;Boden M;Buske FA;Frith M;Grant CE;Clementi L;Ren J;Li WW;Noble WS
通讯作者：
Noble WS
影响因子：
30.8
作者：
通讯作者：
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