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首页> 外文期刊>Epigenetics & Chromatin >The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis
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The histone 3 lysine 4 methyltransferase, Mll2, is only required briefly in development and spermatogenesis

机译：组蛋白3赖氨酸4甲基转移酶Mll2仅在发育和精子发生中短暂需要

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Background Histone methylation is thought to be central to the epigenetic mechanisms that maintain and confine cellular identity in multi-cellular organisms. To examine epigenetic roles in cellular homeostasis, we conditionally mutated the histone 3 lysine 4 methyltransferase, Mll2, in embryonic stem (ES) cells, during development and in adult mice using tamoxifen-induced Cre recombination. Results In ES cells, expression profiling unexpectedly revealed that only one gene, Magoh2, is dependent upon Mll2 and few other genes were affected. Loss of Mll2 caused loss of H3K4me3 at the Magoh2 promoter and concomitant gain of H3K27me3 and DNA methylation. Hence Mll2, which is orthologous to Drosophila Trithorax, is required to prevent Polycomb-Group repression of the Magoh2 promoter, and repression is further accompanied by DNA methylation. Early loss of Mll2 in utero recapitulated the embryonic lethality found in Mll2-/- embryos. However, loss of Mll2 after E11.5 produced mice without notable pathologies. Hence Mll2 is not required for late development, stem cells or homeostasis in somatic cell types. However it is required in the germ cell lineage. Spermatogenesis was lost upon removal of Mll2, although spermatogonia A persisted. Conclusion These data suggest a bimodal recruit and maintain model whereby Mll2 is required to establish certain epigenetic decisions during differentiation, which are then maintained by redundant mechanisms. We also suggest that these mechanisms relate to the epigenetic maintenance of CpG island promoters.
机译：背景技术组蛋白甲基化被认为是在多细胞生物体中维持和限制细胞特性的表观遗传机制的核心。为了检查表观遗传学在细胞稳态中的作用，我们使用他莫昔芬诱导的Cre重组在胚胎干（ES）细胞，发育期间和成年小鼠中有条件地突变了组蛋白3赖氨酸4甲基转移酶Mll2。结果在ES细胞中，表达谱出乎意料地揭示出只有一个基因Magoh2依赖于Mll2，而其他几个基因也没有受到影响。 Mll2的丢失导致Magoh2启动子处的H3K4me3丢失，并伴随H3K27me3的获得和DNA甲基化。因此，需要与果蝇Trithoorax同源的Mll2来防止Magoh2启动子的多梳基团阻遏，并且阻遏还伴随着DNA甲基化。子宫内Mll2的早期丢失概括了Mll2-/-胚胎中的胚胎致死率。但是，E11.5后Mll2的丢失产生了没有明显病理的小鼠。因此，体细胞类型中的后期发育，干细胞或体内稳态不需要Mll2。但是，生殖细胞谱系是必需的。尽管去除了Mll2，但精子A仍然存在，精子发生消失了。结论这些数据表明了双峰募集和维持模型，在分化过程中需要Mll2建立某些表观遗传决定，然后通过冗余机制对其进行维持。我们还建议这些机制与CpG岛启动子的表观遗传维持有关。

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