ATF7IP2, a meiosis-specific partner of SETDB1, is required for proper chromosome remodeling and crossover formation during spermatogenesis
Qiqi Shao,
Yanan Zhang,
Yanlei Liu,
Yongliang Shang,
Si Li,
Lin Liu,
Guoqiang Wang,
Xu Zhou,
Ping Wang,
Jinmin Gao,
Jun Zhou,
Liangran Zhang,
Shunxin Wang
Affiliations
Qiqi Shao
Center for Reproductive Medicine, State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong 250012, China
Yanan Zhang
Center for Reproductive Medicine, State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong 250012, China
Yanlei Liu
Center for Reproductive Medicine, State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong 250012, China
Yongliang Shang
Advanced Medical Research Institute, Shandong University, Jinan, Shandong 250012, China
Si Li
Advanced Medical Research Institute, Shandong University, Jinan, Shandong 250012, China
Lin Liu
Center for Reproductive Medicine, State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong 250012, China
Guoqiang Wang
Advanced Medical Research Institute, Shandong University, Jinan, Shandong 250012, China
Xu Zhou
Advanced Medical Research Institute, Shandong University, Jinan, Shandong 250012, China
Ping Wang
Center for Reproductive Medicine, State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong 250012, China
Jinmin Gao
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan 250014, Shandong, China
Jun Zhou
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan 250014, Shandong, China
Liangran Zhang
Advanced Medical Research Institute, Shandong University, Jinan, Shandong 250012, China; Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan 250014, Shandong, China; Corresponding author
Shunxin Wang
Center for Reproductive Medicine, State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong 250012, China; Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong 250012, China; Corresponding author
Summary: 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.
