增强子 HS2 在 T(H)2 细胞中对 GATA-3 介导的 Il4 转录起关键调控作用。
The enhancer HS2 critically regulates GATA-3-mediated Il4 transcription in T(H)2 cells.
机构信息
Laboratory for Signal Network, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan.
出版信息
Nat Immunol. 2011 Jan;12(1):77-85. doi: 10.1038/ni.1966. Epub 2010 Dec 5.
GATA-3 is a master regulator of T helper type 2 (T(H)2) differentiation. However, the molecular basis of GATA-3-mediated T(H)2 lineage commitment is poorly understood. Here we identify the DNase I-hypersensitive site 2 (HS2) element located in the second intron of the interleukin 4 locus (Il4) as a critical enhancer strictly controlled by GATA-3 binding. Mice lacking HS2 showed substantial impairment in their asthmatic responses and their production of IL-4 but not of other T(H)2 cytokines. Overexpression of Gata3 in HS2-deficient T cells failed to restore Il4 expression. HS2 deletion impaired the trimethylation of histone H3 at Lys4 and acetylation of histone H3 at Lys9 and Lys14 in the Il4 locus. Our results indicate that HS2 is the target of GATA-3 in regulating chromosomal modification of the Il4 locus and is independent of the Il5 and Il13 loci.
GATA-3 是 T 辅助细胞 2（T(H)2）分化的主调控因子。然而，GATA-3 介导的 T(H)2 谱系定向的分子基础理解得还很差。在这里，我们确定了位于白细胞介素 4 基因座（Il4）第二个内含子中的 DNase I 超敏位点 2（HS2）元件，作为一个由 GATA-3 结合严格控制的关键增强子。缺乏 HS2 的小鼠在其哮喘反应和 IL-4 的产生方面存在显著缺陷，但其他 T(H)2 细胞因子不受影响。在 HS2 缺陷的 T 细胞中过表达 Gata3 未能恢复 Il4 的表达。HS2 缺失损害了 Il4 基因座处组蛋白 H3 赖氨酸 4 的三甲基化和组蛋白 H3 赖氨酸 9 和赖氨酸 14 的乙酰化。我们的结果表明，HS2 是 GATA-3 调节 Il4 基因座染色质修饰的靶点，并且独立于 Il5 和 Il13 基因座。
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