Twist1 通过干扰 Runx3 的功能调节 Th1 细胞中的 Ifng 表达。
Twist1 regulates Ifng expression in Th1 cells by interfering with Runx3 function.
机构信息
Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
出版信息
J Immunol. 2012 Jul 15;189(2):832-40. doi: 10.4049/jimmunol.1200854. Epub 2012 Jun 8.
Abstract
A transcription factor network that includes STAT4, T-bet, and Runx3 promotes the differentiation of Th1 cells and inflammatory immune responses. How additional transcription factors regulate the function of Th1 cells has not been defined. In this study we show that the negative regulatory factor Twist1 decreases expression of T-bet, Runx3, and IL-12Rβ2 as it inhibits IFN-γ production. Ectopic expression of Runx3, but not T-bet or IL-12Rβ2, compensates for the effects of Twist1 on IFN-γ production, and Twist1 regulation of Ifng depends on complex formation with Runx3. Twist1 decreases Runx3 and T-bet binding at the Ifng locus, and it decreases chromatin looping within the Ifng locus. These data define an IL-12/STAT4-induced negative regulatory loop that impacts multiple components of the Th1 transcriptional network and provide further insight into regulation of Th1 differentiation.
摘要
一个包含 STAT4、T-bet 和 Runx3 的转录因子网络促进了 Th1 细胞的分化和炎症免疫反应。然而，其他转录因子如何调节 Th1 细胞的功能尚未确定。在这项研究中，我们发现负调控因子 Twist1 通过抑制 IFN-γ 的产生，降低 T-bet、Runx3 和 IL-12Rβ2 的表达。Runx3 的异位表达，而不是 T-bet 或 IL-12Rβ2，可补偿 Twist1 对 IFN-γ 产生的影响，并且 Twist1 对 Ifng 的调控依赖于与 Runx3 的复合物形成。 Twist1 降低了 Ifng 基因座处的 Runx3 和 T-bet 结合，并降低了 Ifng 基因座内的染色质环化。这些数据定义了一个由 IL-12/STAT4 诱导的负反馈调节环，影响 Th1 转录网络的多个组件，并进一步深入了解 Th1 分化的调控。
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