Nucleosome positioning can alter the accessibility of DNA-binding proteins to their cognate DNA elements, and thus its precise control is essential for cell identity and function. Mammalian preimplantation embryos undergo temporal changes in gene expression and cell potency, suggesting the involvement of dynamic epigenetic control during this developmental phase. However, the dynamics of nucleosome organization during early development are poorly understood. In this study, using a low-input MNase-seq method, we show that nucleosome positioning is globally obscure in zygotes but becomes well defined during subsequent development. Down-regulation of the chromatin assembly in embryonic stem cells can partially reverse nucleosome organization into a zygote-like pattern, suggesting a possible link between the chromatin assembly pathway and fuzzy nucleosomes in zygotes. We also reveal that YY1, a zinc finger-containing transcription factor expressed upon zygotic genome activation, regulates the de novo formation of well-positioned nucleosome arrays at the regulatory elements through identifying YY1-binding sites in eight-cell embryos. The YY1-binding regions acquire H3K27ac enrichment around the eight-cell and morula stages, and YY1 depletion impairs the morula-to-blastocyst transition. Thus, our study delineates the remodeling of nucleosome organization and its underlying mechanism during early mouse development.

中文翻译：

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YY1介导的动态核小体重塑是小鼠早期发育的基础

核小体定位可以改变 DNA 结合蛋白与其同源 DNA 元件的可及性，因此其精确控制对于细胞身份和功能至关重要。哺乳动物植入前胚胎的基因表达和细胞效力经历时间变化，表明在该发育阶段涉及动态表观遗传控制。然而，人们对早期发育过程中核小体组织的动态知之甚少。在本研究中，使用低输入 MNase-seq 方法，我们表明核小体定位在受精卵中全局模糊，但在后续发育过程中变得明确。胚胎干细胞中染色质组装的下调可以部分地将核小体组织逆转为受精卵样模式，这表明染色质组装途径与受精卵中的模糊核小体之间可能存在联系。我们还揭示了 YY1（一种在合子基因组激活时表达的含锌指转录因子）通过识别八细胞胚胎中的 YY1 结合位点来调节调节元件处良好定位的核小体阵列的从头形成。YY1 结合区域在八细胞和桑椹胚阶段周围获得 H3K27ac 富集，而 YY1 耗尽会损害桑葚胚向囊胚的转变。因此，我们的研究描述了小鼠早期发育过程中核小体组织的重塑及其潜在机制。