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首页> 外文期刊>Molecular biology of the cell >Requirement for down-regulation of the CCAAT-binding activity of the NF-Y transcription factor during skeletal muscle differentiation
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Requirement for down-regulation of the CCAAT-binding activity of the NF-Y transcription factor during skeletal muscle differentiation

机译:在骨骼肌分化过程中下调NF-Y转录因子CCAAT结合活性的要求

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摘要

NF-Y is composed of three subunits, NF-YA, NF-YB, and NF-YC, all required for DNA binding. All subunits are expressed in proliferating skeletal muscle cells, whereas NF-YA alone is undetectable in terminally differentiated cells in vitro. By immunohistochemistry, we show that the NF-YA protein is not expressed in the nuclei of skeletal and cardiac muscle cells in vivo. By chromatin immunoprecipitation experiments, we demonstrate herein that NF-Y does not bind to the CCAAT boxes of target promoters in differentiated muscle cells. Consistent with this, the activity of these promoters is down-regulated in differentiated muscle cells. Finally, forced expression of the NF-YA protein in cells committed to differentiate leads to an impairment in the down-regulation of cyclin A, cyclin B1, and cdk1 expression and is accompanied by a delay in myogenin expression. Thus, our results indicate that the suppression of NF-Y function is of crucial importance for the inhibition of several cell cycle genes and the induction of the early muscle-specific program in postmitotic muscle cells. [References: 44]
机译:NF-Y由三个亚基NF-YA,NF-YB和NF-YC组成,它们都是DNA结合所必需的。所有亚基均在增生的骨骼肌细胞中表达,而仅NF-YA在体外终分化细胞中无法检测到。通过免疫组织化学,我们显示在体内骨骼肌和心肌细胞的核中不表达NF-YA蛋白。通过染色质免疫沉淀实验,我们在这里证明了NF-Y在分化的肌肉细胞中不结合靶标启动子的CCAAT盒。与此相一致,这些启动子的活性在分化的肌肉细胞中被下调。最后,在致力于分化的细胞中强迫表达NF-YA会导致细胞周期蛋白A,细胞周期蛋白B1和cdk1表达的下调受损,并伴有肌生成素表达的延迟。因此,我们的结果表明,抑制NF-Y功能对于抑制几个细胞周期基因和诱导有丝分裂后的肌肉细胞中早期肌肉特异性程序至关重要。 [参考:44]

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