BCL11B participates in the activation of IL2 gene expression in CD4+ T lymphocytes
BCL11B participates in the activation of IL2 gene expression in CD4+ T lymphocytes
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DOI：
10.1182/blood-2006-05-021790
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发表时间：
2006-10-15
期刊：
影响因子：
20.3
通讯作者：
Avram, Dorina
中科院分区：
文献类型：
--
作者：
Cismasiu, Valeriu B.;Ghanta, Sailaja;Avram, Dorina
BCL11A 和 BCL11B 是对淋巴细胞生成很重要的转录调节因子，之前与造血系统恶性肿瘤相关。小鼠 Bcl11b 基因座的消融导致无法产生双阳性胸腺细胞，这表明 Bcl11b 在 T 细胞发育中发挥着关键作用。然而，BCL11B 也在静息和激活状态下的 CD4(+) T 淋巴细胞中表达。在这里，我们在转化的和原代的 CD4(+) T 细胞中显示，BCL11 B 在通过 T 细胞受体 (TCR) 激活后参与白细胞介素 2 (IL2) 基因表达的控制。 BCL11 B 通过直接结合 US1 位点增强 IL2 启动子的表达。此外，BCL11 B 与通过 TCR 激活的 CD4(+) T 细胞中的 p300 共激活因子相关，这可能解释了其转录激活功能。这些结果提供了第一个证据，证明 BCL11B（最初被描述为转录阻遏蛋白）在 T 细胞激活的情况下激活靶基因的转录。
BCL11A and BCL11B are transcriptional regulators important for lymphopoiesis and previously associated with hematopoletic malignancies. Ablation of the mouse Bcl11b locus results in failure to generate double-positive thymocytes, implicating a critical role of Bcl11b in T-cell development. However, BCL11B is also expressed in CD4(+) T lymphocytes, both in resting and activated states. Here we show both in transformed and primary CD4(+) T cells that BCL11 B participates in the control of the interleukin-2 (IL2) gene expression following activation through T-cell receptor (TCR). BCL11 B augments expression from the IL2promoter through direct binding to the US1 site. In addition, BCL11 B associates with the p300 coactivator in CD4(+) T cells activated through TCR, which may account for its transcriptional activation function. These results provide the first evidence that BCL11B, originally described as a transcriptional repressor, activates transcription of a target gene in the context of T-cell activation.