Institute for Immunobiology, Department of Immunology, Shanghai Medical College of Fudan University, Shanghai 200032, PR China.
Biochem Biophys Res Commun. 2011 Jul 8;410(3):549-54. doi: 10.1016/j.bbrc.2011.06.022. Epub 2011 Jun 12.
The modification of chromatin structure is increasingly recognized to be an important facet of transcriptional regulation. Here, we report that Brahma-related gene 1 (BRG1), a chromatin remodeling enzyme, plays a crucial role in IFN-γ-induced TRIM22 expression. Our results showed that IFN-γ failed to induce TRIM22 expression in BRG1-deficient SW-13 cells, and reconstitution of BRG1 in this cell line could restore IFN-γ induction of TRIM22. Furthermore, it was revealed that BRG1 absence, per se, did not impair IFN-γ-induced IRF-1 expression, but blocked its access to TRIM22 promoter, and BRG1-dependent induction of TRIM22 perfectly correlated with BRG1-dependent recruitment of IRF-1 to TRIM22 promoter. We also found that the DNA-dependent ATPase domain of BRG1 was required for TRIM22 expression and IRF-1 recruitment in response to IFN-γ stimulation, suggesting that BRG1-mediated chromatin remodeling is critical for the IFN-γ-inducibility of TRIM22 gene.
染色质结构的修饰逐渐被认为是转录调控的一个重要方面。在这里，我们报告 BRG1（一种染色质重塑酶）在 IFN-γ 诱导的 TRIM22 表达中起着关键作用。我们的结果表明，IFN-γ 不能诱导 BRG1 缺陷的 SW-13 细胞中 TRIM22 的表达，而在该细胞系中重建 BRG1 可以恢复 IFN-γ 诱导的 TRIM22。此外，研究表明，BRG1 的缺失本身并不会损害 IFN-γ 诱导的 IRF-1 表达，但会阻止其进入 TRIM22 启动子，并且 BRG1 依赖性的 TRIM22 诱导与 BRG1 依赖性的 IRF-1 募集到 TRIM22 启动子完全相关。我们还发现，BRG1 的 DNA 依赖性 ATP 酶结构域对于 IFN-γ 刺激时的 TRIM22 表达和 IRF-1 募集是必需的，这表明 BRG1 介导的染色质重塑对于 TRIM22 基因的 IFN-γ 诱导至关重要。
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