Two DNA binding domains of Mga act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells
Two DNA binding domains of Mga act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells
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DOI：
10.1002/stem.3433
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发表时间：
2020-07
期刊：
影响因子：
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通讯作者：
Kousuke Uranishi;Masataka Hirasaki;Y. Kitamura;Y. Mizuno;M. Nishimoto;Ayumu Suzuki;A. Okuda
中科院分区：
文献类型：
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作者：
Kousuke Uranishi;Masataka Hirasaki;Y. Kitamura;Y. Mizuno;M. Nishimoto;Ayumu Suzuki;A. Okuda
小鼠胚胎干细胞(ESCs)像生殖细胞一样，具有很高的进入减数分裂的潜力。虽然这种潜力的生理意义尚不清楚，但可以肯定的是，需要一个严格的保护系统来防止异位减数分裂的发生。PRC1.6是一种非规范的PRC1，在生殖细胞和ESCs中分别以抑制早熟和异位减数分裂而闻名，其中MGA在DNA结合和构建复合体作为支架成分方面发挥着重要作用。作为一个显著的特征，MGA含有两个不同的DNA结合域，分别称为bHLHZ和T-box。然而，这些特征如何影响PRC1.6的功能，特别是在抑制减数分裂基因方面，仍然很大程度上是未知的。在这里，我们证明了MGA的DNA结合域都抑制了小鼠胚胎干细胞中不同的基因集，并且在两个基因集中都包括了大量与减数分裂相关的基因。此外，我们的数据表明，MGA的两个DNA结合域，特别是bHLHZ，都关键地参与了抑制Meiosin的表达，Meiosin在与Stra8协同进入减数分裂过程中起着至关重要的作用，揭示了至少部分联系减数分裂开始的负调控和正调控的分子机制。
Mouse embryonic stem cells (ESCs) have high potential for meiotic entry, like germ cells. Although the physiological meaning of this potential is not known, it is certain that a rigid safeguarding system is required to prevent ectopic onset of meiosis. PRC1.6, a non-canonical PRC1, is known for its suppression of precocious and ectopic meiotic onset in germ cells and ESCs, respectively, in which MGA has important roles in DNA binding as well as in constructing the complex as a scaffolding component. As a salient feature, MGA bears two distinct DNA-binding domains termed bHLHZ and T-box. However, how these features contribute to the functions of PRC1.6, particularly in the repression of meiotic genes, remains largely obscure. Here, we demonstrated that both DNA binding domains of Mga repress distinct sets of genes in murine ESCs, and substantial numbers of meiosis-related genes are included in both gene sets. In addition, our data demonstrated that both DNA binding domains of Mga, in particular bHLHZ, are crucially involved in repressing the expression of Meiosin, which plays essential roles in meiotic entry in collaboration with Stra8, revealing at least part of the molecular mechanisms that link negative and positive regulation of meiotic onset.