Center for Reproductive Medicine, State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong 250012, China.
Advanced Medical Research Institute, Shandong University, Jinan, Shandong 250012, China.
Cell Rep. 2023 Aug 29;42(8):112953. doi: 10.1016/j.celrep.2023.112953. Epub 2023 Aug 4.
Meiotic crossovers are required for the faithful segregation of homologous chromosomes and to promote genetic diversity. However, it is unclear how crossover formation is regulated, especially on the XY chromosomes, which show a homolog only at the tiny pseudoautosomal region. Here, we show that ATF7IP2 is a meiosis-specific ortholog of ATF7IP and a partner of SETDB1. In the absence of ATF7IP2, autosomes show increased axis length and more crossovers; however, many XY chromosomes lose the obligatory crossover, although the overall XY axis length is also increased. Additionally, meiotic DNA double-strand break formation/repair may also be affected by altered histone modifications. Ultimately, spermatogenesis is blocked, and male mice are infertile. These findings suggest that ATF7IP2 constraints autosomal axis length and crossovers on autosomes; meanwhile, it also modulates XY chromosomes to establish meiotic sex chromosome inactivation for cell-cycle progression and to ensure XY crossover formation during spermatogenesis.
减数分裂交叉是同源染色体正确分离和促进遗传多样性所必需的。然而，交叉形成如何被调控尚不清楚，特别是在 XY 染色体上，其仅在微小的假常染色体区域具有同源物。在这里，我们表明 ATF7IP2 是 ATF7IP 的减数分裂特异性同源物，也是 SETDB1 的伴侣。在缺乏 ATF7IP2 的情况下，常染色体显示出轴长增加和更多的交叉；然而，许多 XY 染色体失去了必需的交叉，尽管总体的 XY 轴长度也增加了。此外，减数分裂 DNA 双链断裂的形成/修复也可能受到组蛋白修饰的改变的影响。最终，精子发生受阻，雄性小鼠不育。这些发现表明，ATF7IP2 限制了常染色体的轴长和交叉；同时，它还调节 XY 染色体，以建立减数分裂性染色体失活，促进细胞周期进程，并确保在精子发生过程中形成 XY 交叉。
