C-elegans HIM-17 links chromatin modification and competence for initiation of meiotic recombination
C-elegans HIM-17 links chromatin modification and competence for initiation of meiotic recombination
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DOI：
10.1016/j.cell.2004.07.026
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发表时间：
2004-08-20
期刊：
影响因子：
64.5
通讯作者：
Villeneuve, AM
中科院分区：
文献类型：
--
作者：
Reddy, KC;Villeneuve, AM
由双链断裂（DSB）引发的减数分裂重组必须以受控的方式发生，以避免危及基因组的完整性。在这里，我们确定了染色质相关蛋白HIM-17作为染色质状态和DSB形成之间的联系，在C。线虫减数分裂HIM-17上的几个减数分裂前期事件的发生与DSB生成酶SPO-11的发生平行：HIM-17对DSB形成是必需的，但对同源突触是不必要的。交叉和交叉在他-17无效突变体中被消除，但通过人工诱导的DSB被恢复，这表明将DSB转化为交叉所需的所有组分都存在。与SPO-11不同，HIM-17也是减数分裂前期染色体上赖氨酸9处组蛋白H3甲基化适当积累所必需的。HIM-17与三种蛋白质具有共同的结构特征，这些蛋白质与染色质修饰复合物的已知成分LIN-35/Rb发生遗传相互作用。此外，DSB水平和交叉的发生率可以通过LIN-35/Rb的缺失来调节。这些和其他数据表明，染色质状态支配DSB能力的时间。
Initiation of meiotic recombination by double-strand breaks (DSBs) must occur in a controlled fashion to avoid jeopardizing genome integrity. Here, we identify chromatin-associated protein HIM-17 as a link between chromatin state and DSB formation during C. elegans meiosis. Dependencies of several meiotic prophase events on HIM-17 parallel those seen for DSB-generating enzyme SPO-11: HIM-17 is essential for DSB formation but dispensable for homolog synapsis. Crossovers and chiasmata are eliminated in him-17 null mutants but are restored by artificially induced DSBs, indicating that all components required to convert DSBs into chiasmata are present. Unlike SPO-11, HIM-17 is also required for proper accumulation of histone H3 methylation at lysine 9 on meiotic prophase chromosomes. HIM-17 shares structural features with three proteins that interact genetically with LIN-35/Rb, a known component of chromatin-modifying complexes. Furthermore, DSB levels and incidence of chiasmata can be modulated by loss of LIN-35/Rb. These and other data suggest that chromatin state governs the timing of DSB competence.