Yang Shu Yuan, Chang Yi-Chieh, Wan Yu Hsin, Whitworth Cale, Baxter Ellen M, Primus Shekerah, Pi Haiwei, Van Doren Mark
Department of Biomedical Sciences, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Genetics. 2017 Aug;206(4):1939-1949. doi: 10.1534/genetics.117.199935. Epub 2017 Jun 6.
A key aspect of germ cell development is to establish germline sexual identity and initiate a sex-specific developmental program to promote spermatogenesis or oogenesis. Previously, we have identified the histone reader Plant Homeodomain Finger 7 (PHF7) as an important regulator of male germline identity. To understand how PHF7 directs sexual differentiation of the male germline, we investigated the downstream targets of PHF7 by combining transcriptome analyses, which reveal genes regulated by , with genomic profiling of histone H3K4me2, the chromatin mark that is bound by PHF7. Through these genomic experiments, we identify a novel spermatocyte factor Receptor Accessory Protein Like 1 (REEPL1) that can promote spermatogenesis and whose expression is kept off by PHF7 in the spermatogonial stage. Loss of significantly rescues the spermatogenesis defects in mutants, indicating that regulation of is an essential aspect of PHF7 function. Further, increasing REEPL1 expression facilitates spermatogenic differentiation. These results indicate that PHF7 controls spermatogenesis by regulating the expression patterns of important male germline genes.
生殖细胞发育的一个关键方面是确立生殖系性别身份,并启动特定性别的发育程序以促进精子发生或卵子发生。此前,我们已确定组蛋白阅读器植物同源结构域指蛋白7(PHF7)是雄性生殖系身份的重要调节因子。为了解PHF7如何指导雄性生殖系的性别分化,我们通过结合转录组分析来研究PHF7的下游靶点,转录组分析揭示了受其调控的基因,同时还对组蛋白H3K4me2进行了基因组分析,H3K4me2是与PHF7结合的染色质标记。通过这些基因组实验,我们鉴定出一种新型精母细胞因子类受体辅助蛋白1(REEPL1),它可促进精子发生,且其表达在精原细胞阶段被PHF7抑制。REEPL1缺失显著挽救了PHF7突变体中的精子发生缺陷,表明对REEPL1的调控是PHF7功能的一个重要方面。此外,增加REEPL1的表达有助于精子发生分化。这些结果表明,PHF7通过调节重要雄性生殖系基因的表达模式来控制精子发生。