Atf7ip2, also known as MCAF2, is a germline-specific protein. It is a critical regulator in male meiosis, playing essential roles in H3K9 methylation, which is involved in gene regulation beyond its presence on pericentric constitutive heterochromatin. Atf7ip2 is associated with the DNA damage response pathway in meiosis and is crucial for spermatogenic heterochromatin organization [1,3].

In male germ cells, Atf7ip2-deficient mice show that in the absence of Atf7ip2, male germ cells are arrested in meiotic prophase I. This reveals its essential functions in maintaining meiotic sex chromosome inactivation (MSCI), suppressing retrotransposons, and globally up-regulating autosomal genes. Also, in Atf7ip2-deficient spermatogenesis, autosomes have increased axis length and more crossovers, while many XY chromosomes lose the obligatory crossover, ultimately leading to blocked spermatogenesis and male infertility. These findings suggest that Atf7ip2 modulates chromosome remodeling and crossover formation during spermatogenesis [1,2,3].

In conclusion, Atf7ip2 is a key regulator in male meiosis, with its function in H3K9 methylation and meiotic gene regulation being essential for normal spermatogenesis. The study of Atf7ip2-deficient mouse models has provided valuable insights into the role of Atf7ip2 in male reproductive processes, highlighting its importance in understanding male infertility and related meiotic disorders.

References:

1. Alavattam, Kris G, Esparza, Jasmine M, Hu, Mengwen, Ishiguro, Kei-Ichiro, Namekawa, Satoshi H. 2024. ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline. In Genes & development, 38, 115-130. doi:10.1101/gad.351569.124. https://pubmed.ncbi.nlm.nih.gov/38383062/

2. Shao, Qiqi, Zhang, Yanan, Liu, Yanlei, Zhang, Liangran, Wang, Shunxin. 2023. ATF7IP2, a meiosis-specific partner of SETDB1, is required for proper chromosome remodeling and crossover formation during spermatogenesis. In Cell reports, 42, 112953. doi:10.1016/j.celrep.2023.112953. https://pubmed.ncbi.nlm.nih.gov/37542719/

3. Alavattam, Kris G, Esparza, Jasmine M, Hu, Mengwen, Ishiguro, Kei-Ichiro, Namekawa, Satoshi H. 2023. ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.09.30.560314. https://pubmed.ncbi.nlm.nih.gov/37873266/