Cell Signaling Coordinates Global PRC2 Recruitment and Developmental Gene Expression in Murine Embryonic Stem Cells.
Cell Signaling Coordinates Global PRC2 Recruitment and Developmental Gene Expression in Murine Embryonic Stem Cells.
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DOI：
10.1016/j.isci.2020.101646
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发表时间：
2020-11-20
期刊：
影响因子：
5.8
通讯作者：
He J
中科院分区：
文献类型：
--
作者：
Aljazi MB;Gao Y;Wu Y;Mias GI;He J
多梳抑制复合体2(PRC2)在抑制小鼠胚胎干细胞(MESCs)基因表达方面发挥着重要作用，其在基因启动子中的募集是至关重要的。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受到抑制，但在幼稚的mESCs中，全基因组的PRC2占有率出人意料地减少。在本研究中，我们提供了证据，证明成纤维细胞生长因子/细胞外信号调节激酶信号通过调节PRC2-Recruiting因子JARID2在幼稚的mESCs中的表达来决定PRC2的全球占有率。在转录水平上，二价基因的下调主要由细胞信号相关转录因子的存在决定，而不是由基因启动子上PRC2的状态决定。因此，本研究不仅揭示了细胞信号调节mESCs中PRC2占位的关键分子机制，而且阐明了转录因子的功能作用和Polycomb介导的表观遗传机制在转录调控中的作用。成纤维细胞生长因子/ERK信号正向调节mESCs中Jarid2的表达JARID2减少导致原始mESCs中PRC2占有率的全局减少仅减少PRC2占有率不足以诱导转录激活细胞信号相关转录因子驱动二价基因表达分子生物学；细胞生物学；干细胞研究；发育生物学
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. FGF/ERK signaling positively regulates Jarid2 expression in mESCs Reduced JARID2 causes global reduction of PRC2 occupancy in naive mESCs Reduced PRC2 occupancy alone is insufficient to induce transcriptional activation Cell signaling-associated transcription factors drive bivalent gene expression Molecular Biology; Cell Biology; Stem Cells Research; Developmental Biology
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影响因子：
16.8
作者：
Leitch, Harry G.;McEwen, Kirsten R.;Turp, Aleksandra;Encheva, Vesela;Carroll, Tom;Grabole, Nils;Mansfield, William;Nashun, Buhe;Knezovich, Jaysen G.;Smith, Austin;Surani, M. Azim;Hajkova, Petra
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Hajkova, Petra
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Blackledge NP;Zhou JC;Tolstorukov MY;Farcas AM;Park PJ;Klose RJ
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Salzberg, Steven L.
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通讯作者：
Klose RJ
影响因子：
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作者：
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通讯作者：
Rossant, Janet