Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University, Seoul 04763, Korea.
Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21936, Korea.
BMB Rep. 2017 Sep;50(9):472-477. doi: 10.5483/bmbrep.2017.50.9.124.
The transcription repressor Bach2 has been proposed as a regulator of T cell quiescence, but the underlying mechanism is not fully understood. Given the importance of interleukin-2 in T cell activation, we investigated whether Bach2 is a component of the network of factors that regulates interleukin-2 expression. In primary and transformed CD4＋ T cells, Bach2 overexpression counteracted T cell receptor/CD28- or PMA/ionomycin-driven induction of interleukin-2 expression, and silencing of Bach2 had the opposite effect. Luciferase and chromatin immunoprecipitation assays revealed that Bach2 binds to multiple Maf-recognition element-like sites on the interleukin-2 proximal promoter in a manner competitive with AP-1, and thereby represses AP-1-driven induction of interleukin-2 transcription. Thus, this study demonstrates that Bach2 is a direct repressor of the interleukin-2 gene in CD4＋ T cells during the immediate early phase of AP-driven activation, thereby playing an important role in the maintenance of immune quiescence in the steady state. [BMB Reports 2017; 50(9): 472-477].
转录抑制因子 Bach2 被认为是 T 细胞静止的调节因子，但其中的作用机制尚不完全清楚。鉴于白细胞介素-2 在 T 细胞激活中的重要性，我们研究了 Bach2 是否是调节白细胞介素-2 表达的网络因素的一部分。在原代和转化的 CD4+T 细胞中，Bach2 的过表达拮抗了 T 细胞受体/CD28 或 PMA/离子霉素驱动的白细胞介素-2 表达诱导，而 Bach2 的沉默则产生相反的效果。荧光素酶和染色质免疫沉淀测定显示，Bach2 以一种与 AP-1 竞争的方式结合到白细胞介素-2 近端启动子上的多个 Maf 识别元件样位点，从而抑制 AP-1 驱动的白细胞介素-2 转录诱导。因此，本研究表明，Bach2 是 CD4+T 细胞中 AP 驱动激活的早期阶段白细胞介素-2 基因的直接抑制剂，从而在稳态下维持免疫静止中发挥重要作用。[BMB 报告 2017;50(9):472-477]。
