Buard Jérôme, Barthès Pauline, Grey Corinne, de Massy Bernard
Institut de Génétique Humaine, CNRS UPR 1142, Montpellier, France.
EMBO J. 2009 Sep 2;28(17):2616-24. doi: 10.1038/emboj.2009.207. Epub 2009 Jul 30.
Little is known about the factors determining the location and activity of the rapidly evolving meiotic crossover hotspots that shape genome diversity. Here, we show that several histone modifications are enriched at the active mouse Psmb9 hotspot, and we distinguish those marks that precede from those that follow hotspot recombinational activity. H3K4Me3, H3K4Me2 and H3K9Ac are specifically enriched in the chromatids that carry an active initiation site, and in the absence of DNA double-strand breaks (DSBs) in Spo11(-/-) mice. We thus propose that these marks are part of the substrate for recombination initiation at the Psmb9 hotspot. In contrast, hyperacetylation of H4 is increased as a consequence of DSB formation, as shown by its dependency on Spo11 and by the enrichment detected on both recombining chromatids. In addition, the comparison with another hotspot, Hlx1, strongly suggests that H3K4Me3 and H4 hyperacetylation are common features of DSB formation and repair, respectively. Altogether, the chromatin signatures of the Psmb9 and Hlx1 hotspots provide a basis for understanding the distribution of meiotic recombination.
关于决定快速进化的减数分裂交叉热点的位置和活性、塑造基因组多样性的因素，人们知之甚少。在此，我们表明几种组蛋白修饰在活跃的小鼠Psmb9热点处富集，并且我们区分了那些在热点重组活性之前和之后出现的标记。H3K4Me3、H3K4Me2和H3K9Ac在携带活跃起始位点的染色单体中特异性富集，且在Spo11(-/-)小鼠中不存在DNA双链断裂（DSB）的情况下也如此。因此，我们提出这些标记是Psmb9热点处重组起始底物的一部分。相比之下，H4的高度乙酰化是DSB形成的结果，这通过其对Spo11的依赖性以及在两条重组染色单体上检测到的富集得以证明。此外，与另一个热点Hlx1的比较强烈表明，H3K4Me3和H4高度乙酰化分别是DSB形成和修复的共同特征。总之，Psmb9和Hlx1热点的染色质特征为理解减数分裂重组的分布提供了基础。
