Mu Weipeng, Starmer Joshua, Shibata Yoichiro, Yee Della, Magnuson Terry
Department of Genetics, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264, USA.
Department of Genetics, and Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7264, USA.
Dev Biol. 2017 Apr 15;424(2):198-207. doi: 10.1016/j.ydbio.2017.02.017. Epub 2017 Feb 28.
We previously reported the requirement of Polycomb Repressive Complex 2 (PRC2) for spermatogenesis through transcriptional repression of somatic genes and meiosis-specific genes. To characterize how PRC2's two methyltransferase subunits, EZH1 and EZH2, regulate histone H3 lysine 27 (H3K27) methylation during germ cell development, we generated mouse models with a germline ablation of EZH1 and/or EHZ2. Only the combined loss of EZH1 and EZH2 caused a depletion of global H3K27me3 marks and meiotic arrest in spermatocytes. Genome-wide analysis of H3K27me3 in spermatogenic cells revealed that a noncanonical EZH1-PRC2 could establish and maintain this histone mark on somatic genes and certain meiotic genes. Consistent with it having active enhancers in testis, Ezh1 was not only abundant in highly differentiated spermatocytes but also in actively proliferating progenitor and stem germ cells. Taken together, our findings suggest that the expression level of Ezh1 determines the restoration of H3K27 methylation in the absence of the canonical EZH2-PRC2.
我们之前报道过，多梳抑制复合物2（PRC2）通过对体细胞基因和减数分裂特异性基因的转录抑制作用，对精子发生是必需的。为了表征PRC2的两个甲基转移酶亚基EZH1和EZH2在生殖细胞发育过程中如何调节组蛋白H3赖氨酸27（H3K27）甲基化，我们构建了EZH1和/或EHZ2生殖系缺失的小鼠模型。只有EZH1和EZH2的联合缺失导致了全基因组H3K27me3标记的缺失以及精母细胞减数分裂停滞。对生精细胞中H3K27me3的全基因组分析表明，一种非经典的EZH1-PRC2可以在体细胞基因和某些减数分裂基因上建立并维持这种组蛋白标记。鉴于Ezh1在睾丸中有活跃的增强子，Ezh1不仅在高度分化的精母细胞中丰富，在活跃增殖的祖细胞和生殖干细胞中也很丰富。综上所述，我们的研究结果表明，在没有经典的EZH2-PRC2的情况下，Ezh1的表达水平决定了H3K27甲基化的恢复。
