Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Genes Immun. 2013 Jan;14(1):7-12. doi: 10.1038/gene.2012.47. Epub 2012 Oct 18.
Recombination-activating gene 1 (Rag1) and Rag2 enzymes are required for T cell receptor assembly and thymocyte development. The mechanisms underlying the transcriptional activation and repression of Rag1 and Rag2 are incompletely understood. The zinc-finger protein, Zfp608, represses Rag1 and Rag2 expression when expressed in thymocytes blocking T-cell maturation. Here we show that the related zinc-finger protein, Zfp609, is necessary for Rag1 and Rag2 expression in developing thymocytes. Zfp608 represses Rag1 and Rag2 expression indirectly by repressing the expression of Zfp609. Thus, the balance of Zfp608 and Zfp609 plays a critical role in regulating Rag1 and Rag2 expression, which may manifest itself not only during development of immature thymocytes into mature T cells but also in generation of the T-cell arm of the adaptive immune system, which does not fully develop until after birth.
重组激活基因 1（Rag1）和 Rag2 酶对于 T 细胞受体的组装和胸腺细胞的发育是必需的。 Rag1 和 Rag2 的转录激活和抑制的机制尚不完全清楚。锌指蛋白 Zfp608 在表达于胸腺细胞时会抑制 Rag1 和 Rag2 的表达，从而阻断 T 细胞成熟。在这里，我们表明，相关的锌指蛋白 Zfp609 对于发育中的胸腺细胞中 Rag1 和 Rag2 的表达是必需的。Zfp608 通过抑制 Zfp609 的表达间接抑制 Rag1 和 Rag2 的表达。因此，Zfp608 和 Zfp609 的平衡在调节 Rag1 和 Rag2 的表达中起着关键作用，这不仅可能在未成熟的胸腺细胞发育成熟 T 细胞的过程中表现出来，而且可能在适应性免疫系统的 T 细胞臂的产生中表现出来，直到出生后，适应性免疫系统的 T 细胞臂才完全发育。
