Hata Kenichiro, Kusumi Maki, Yokomine Takaaki, Li En, Sasaki Hiroyuki
Department of Integrated Genetics, Division of Human Genetics, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Japan.
Mol Reprod Dev. 2006 Jan;73(1):116-22. doi: 10.1002/mrd.20387.
The DNA methyltransferase-like protein Dnmt3L is necessary for the establishment of genomic imprints in oogenesis and for normal spermatogenesis (Bourc'his et al., 2001; Hata et al., 2002). Also, a paternally imprinted gene, H19, loses DNA methylation in Dnmt3L-/- spermatogonia (Bourc'his and Bestor, 2004; Kaneda et al., 2004). To determine the reason for the impaired spermatogenesis in the Dnmt3L-/- testes, we have carried out a series of histological and molecular studies. We show here that Dnmt3L-/- germ cells were arrested and died around the early meiotic stage. A microarray-based gene expression-profiling analysis revealed that various gonad-specific and/or sex-chromosome-linked genes were downregulated in the Dnmt3L-/- testes. In contrast, expression of retrovirus-like intracisternal A-particle (IAP) sequences was upregulated; consistent with this observation, a specific IAP copy showed complete loss of DNA methylation. These findings indicate that Dnmt3L regulates germ cell-specific gene expression and IAP suppression, which are critical for male germ cell proliferation and meiosis.
DNA甲基转移酶样蛋白Dnmt3L对于卵子发生过程中基因组印记的建立以及正常精子发生是必需的（布尔希斯等人，2001年；羽田等人，2002年）。此外，一个父系印记基因H19在Dnmt3L基因敲除的精原细胞中失去DNA甲基化（布尔希斯和贝斯特，2004年；金田等人，2004年）。为了确定Dnmt3L基因敲除小鼠睾丸中精子发生受损的原因，我们进行了一系列组织学和分子研究。我们在此表明，Dnmt3L基因敲除的生殖细胞在减数分裂早期阶段左右停滞并死亡。基于微阵列的基因表达谱分析显示，各种性腺特异性和/或性染色体连锁基因在Dnmt3L基因敲除的睾丸中表达下调。相反，逆转录病毒样的胞内A颗粒（IAP）序列的表达上调；与此观察结果一致，一个特定的IAP拷贝显示DNA甲基化完全丧失。这些发现表明，Dnmt3L调节生殖细胞特异性基因表达和IAP抑制，这对雄性生殖细胞增殖和减数分裂至关重要。
