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YY1 Is Required for Posttranscriptional Stability of SOX2 and OCT4 Proteins

机译:YY1是SOX2和OCT4蛋白质转录后稳定性所需的

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摘要

Yinyang1 (YY1) participates in protein-DNA, protein-RNA, and protein–protein interactions and regulates developmental processes and disease mechanisms. YY1 interactions regulate a range of important biological functions, including oocyte maturation, epithelial to mesenchymal transition, and vascular endothelial growth factor (VEGF) signaling. We tested the hypothesis that YY1 is required for inner cell mass (ICM) lineage commitment during preimplantation development. In this study, we document gene expression patterns and protein localization of key transcription factors in Yy1 global, tissue-specific, and dsRNA-mediated knockout/down embryos. YY1 protein was found in cells of preimplantation and peri-implantation embryos, and adult tissues where two isoforms are observed. In the absence of YY1, OCT4 and SOX2 protein were lost in the ICM during preimplantation and naive neuroectoderm during gastrulation stages, yet no difference in Oct4 or Sox2 mRNA levels was observed. The loss of OCT4 and SOX2 protein occurred specifically in cells that normally express both OCT4 and SOX2 protein. These observations support a role for YY1 meditating and/or regulating the interaction of OCT4 and SOX2 at a posttranscriptional level. Our results suggest that distinct mechanisms of YY1-mediated molecular regulation are present in the early embryo, and may offer insight to promote lineage commitment in in vitro cell lines.
机译:阴阳1(YY1)参与蛋白质-DNA,蛋白质-RNA和蛋白质-蛋白质的相互作用,并调节发育过程和疾病机制。 YY1相互作用调节了一系列重要的生物学功能,包括卵母细胞成熟,上皮向间质转化以及血管内皮生长因子(VEGF)信号传导。我们测试了在植入前发育过程中内部细胞团(ICM)谱系承诺需要YY1的假设。在这项研究中,我们记录了Yy1全局,组织特异性和dsRNA介导的敲除/敲除胚胎中关键转录因子的基因表达模式和蛋白质定位。在植入前和植入前后的胚胎细胞以及成年组织中发现了两种同工型,发现了YY1蛋白。在没有YY1的情况下,ICM在植入前和在胃泌乳阶段的幼稚神经外胚层中均丢失了OCT4和SOX2蛋白,但未观察到Oct4或Sox2 mRNA水平的差异。 OCT4和SOX2蛋白的丢失特别发生在通常同时表达OCT4和SOX2蛋白的细胞中。这些观察结果支持YY1在转录后水平上冥想和/或调节OCT4与SOX2的相互作用。我们的结果表明,YY1介导的分子调控的不同机制存在于早期胚胎中,并可能提供洞察力以促进体外细胞系中的谱系定型。

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