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Cell Signaling Coordinates Global PRC2 Recruitment and Developmental Gene Expression in Murine Embryonic Stem Cells

机译:细胞信号传导坐标在鼠胚胎干细胞中坐标坐标全局PRC2募集和发育基因表达

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摘要

The recruitment of Polycomb repressive complex 2 (PRC2) to gene promoters is critical for its function in repressing gene expression in murine embryonic stem cells (mESCs). However, previous studies have demonstrated that although the expression of early lineage-specific genes is largely repressed, the genome-wide PRC2 occupancy is unexpectedly reduced in naive mESCs. In this study, we provide evidence that fibroblast growth factor/extracellular signal-regulated kinase signaling determines the global PRC2 occupancy through regulating the expression of PRC2-recruiting factor JARID2 in naive mESCs. At the transcriptional level, the de-repression of bivalent genes is predominantly determined by the presence of cell signaling-associated transcription factors but not the status of PRC2 occupancy at gene promoters. Hence, this study not only reveals a key molecular mechanism by which cell signaling regulates the PRC2 occupancy in mESCs but also elucidates the functional roles of transcription factors and Polycomb-mediated epigenetic mechanisms in transcriptional regulation.
机译:对基因启动子的Polycomb抑制复合物2(PRC2)的募集对于其在鼠胚胎干细胞(MESCS)中的基因表达中的作用至关重要。然而,先前的研究表明,尽管早期谱系特异性基因的表达在很大程度上被压抑,但是在幼稚的MESC中出乎意料地降低了基因组的PRC2占用率。在这项研究中,我们提供了通过调节Naive MESCS中PRC2招生因子JARID2的表达来确定全球PRC2占用的证据。在转录水平上,通过细胞信号相关的转录因子存在,但不是基因启动子的PRC2占用的状态,主要决定了二价基因的抑制。因此,本研究不仅揭示了细胞信号传导调节MESCS中的PRC2占用的关键分子机制,而且还阐明了转录因子和Polycomb介导的转录调控中的功能作用。

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