YY1 Is Required for Posttranscriptional Stability of SOX2 and OCT4 Proteins.
YY1 Is Required for Posttranscriptional Stability of SOX2 and OCT4 Proteins.
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DOI：
10.1089/cell.2017.0002
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发表时间：
2017-08
影响因子：
1.6
通讯作者：
M. Wallingford;J. Hiller;Kun Zhang;J. Mager
中科院分区：
文献类型：
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作者：
M. Wallingford;J. Hiller;Kun Zhang;J. Mager
阴阳1号（Yinyang 1，YY 1）参与蛋白质-DNA、蛋白质-RNA、蛋白质-蛋白质相互作用，调节发育过程和疾病机制。YY 1相互作用调节一系列重要的生物学功能，包括卵母细胞成熟、上皮细胞向间充质细胞转化和血管内皮生长因子（VEGF）信号传导。我们测试的假设，YY 1是所需的内细胞团（ICM）谱系承诺在植入前的发展。在这项研究中，我们记录了基因表达模式和蛋白质定位的关键转录因子在YY 1全球，组织特异性，dsRNA介导的敲除/下胚胎。YY 1蛋白存在于植入前和植入期胚胎的细胞中，以及观察到两种亚型的成人组织中。在YY 1，OCT 4和SOX 2蛋白丢失的ICM在植入前和幼稚神经外胚层在原肠胚阶段，但没有观察到差异的Oct 4或Sox 2的mRNA水平。OCT 4和SOX 2蛋白的丢失特别发生在正常表达OCT 4和SOX 2蛋白的细胞中。这些观察结果支持YY 1在转录后水平上调节和/或调节OCT 4和SOX 2的相互作用的作用。我们的研究结果表明，YY 1介导的分子调控的不同机制存在于早期胚胎，并可能提供洞察力，以促进在体外细胞系的谱系承诺。
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.