Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi 400-8510, Japan.
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
Genes Dev. 2023 Jul 1;37(13-14):590-604. doi: 10.1101/gad.350376.122. Epub 2023 Aug 2.
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.
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。哺乳动物的胚胎在基因表达和细胞潜能方面经历了时间上的变化，这表明在这个发育阶段存在动态的表观遗传控制。然而，早期发育过程中核小体组织的动态变化还知之甚少。在这项研究中，我们使用低输入 MNase-seq 方法，表明受精卵中的核小体定位是全局模糊的，但在随后的发育过程中变得清晰。胚胎干细胞中染色质组装的下调可以部分将核小体组织转化为受精卵样模式，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，通过在八细胞胚胎中识别 YY1 结合位点，调节新形成的位于调控元件的定位良好的核小体阵列。YY1 结合区域在八细胞和桑椹胚阶段获得 H3K27ac 富集，而 YY1 缺失会损害桑椹胚到囊胚的过渡。因此，我们的研究描绘了早期小鼠发育过程中核小体组织重塑及其潜在机制。
