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首页> 外文期刊>Epigenetics & Chromatin >STAT3 acts through pre-existing nucleosome-depleted regions bound by FOS during an epigenetic switch linking inflammation to cancer
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STAT3 acts through pre-existing nucleosome-depleted regions bound by FOS during an epigenetic switch linking inflammation to cancer

机译：STAT3通过将炎症与癌症联系在一起的表观遗传转换过程，通过FOS结合的预先存在的核小体耗尽区域发挥作用

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Background Transient induction of the Src oncoprotein in a non-transformed breast cell line can initiate an epigenetic switch to a cancer cell via a positive feedback loop that involves activation of the signal transducer and activator of transcription 3 protein (STAT3) and NF-κB transcription factors. Results We show that during the transformation process, nucleosome-depleted regions (defined by formaldehyde-assisted isolation of regulatory elements (FAIRE)) are largely unchanged and that both before and during transformation, STAT3 binds almost exclusively to previously open chromatin regions. Roughly, a third of the transformation-inducible genes require STAT3 for the induction. STAT3 and NF-κB appear to drive the regulation of different gene sets during the transformation process. Interestingly, STAT3 directly regulates the expression of NFKB1, which encodes a subunit of NF-κB, and IL6, a cytokine that stimulates STAT3 activity. Lastly, many STAT3 binding sites are also bound by FOS and the expression of several AP-1 factors is altered during transformation in a STAT3-dependent manner, suggesting that STAT3 may cooperate with AP-1 proteins. Conclusions These observations uncover additional complexities to the inflammatory feedback loop that are likely to contribute to the epigenetic switch. In addition, gene expression changes during transformation, whether driven by pre-existing or induced transcription factors, occur largely through pre-existing nucleosome-depleted regions.
机译：背景Src癌蛋白在未转化的乳腺癌细胞系中的短暂诱导可通过正反馈回路启动表观遗传学转换为癌细胞，该正反馈回路涉及信号转导子和转录3蛋白（STAT3）和NF-κB转录激活子的激活。因素。结果我们显示，在转化过程中，核小体耗尽的区域（由甲醛辅助分离的调控元件（FAIRE）定义）基本保持不变，并且在转化之前和期间，STAT3几乎都与以前开放的染色质区域结合。大约有三分之一的转化诱导基因需要STAT3进行诱导。 STAT3和NF-κB似乎在转化过程中驱动不同基因集的调控。有趣的是，STAT3直接调节编码NF-κB亚基的NFKB1和刺激STAT3活性的细胞因子IL6的表达。最后，许多STAT3结合位点也被FOS结合，并且在转化过程中以STAT3依赖性方式改变了几种AP-1因子的表达，这表明STAT3可能与AP-1蛋白协同作用。结论这些发现揭示了炎症反馈回路的其他复杂性，这些复杂性可能有助于表观遗传转换。另外，转化过程中的基因表达变化，无论是由预先存在的转录因子还是诱导的转录因子驱动，都主要通过预先存在的核小体耗尽区域发生。

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