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通过附近的沉声器对αβ细胞受体基因的αβ系特异表达

A Winoto¹, D Baltimore

¹Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142.

|November 17, 1989

概括

负调节元素控制T细胞受体α基因表达,确保不同的αβ和gamma delta T细胞系. 这些沉声器限制了增强剂的活性,这对于特定基因调节至关重要.

科学领域:

免疫学免疫学免疫学
分子生物学分子生物学
遗传学是一个遗传学.

背景情况:

T细胞是表达阿尔法-β或玛-三角T细胞受体 (TCRs) 的独特血统.
一个单独的位点编码TCRα和delta基因,需要精确的调节,以防止α基因表达在gamma delta T细胞中.

研究的目的:

调查确保T细胞中血统特异性基因表达的调控机制.
在不同的T细胞系中识别控制TCRα基因表达的元素.

主要方法:

分析不同T细胞系中的增强剂活性.
在TCRα基因位点附近的cis作用负调节元件的识别和表征.

主要成果:

最小的TCRα增强剂在玛三角型T细胞中活跃,但在αβ型T细胞中通过负性cis作用元素被静止.
位于Cα基因3'的几个独立于方向和距离的沉声器介导了这种谱系特异性.
这些沉声器还限制了逆转录病毒增强剂的活性,将其限制在αβT细胞中.
阿尔法沉声器在非T细胞系中起作用,这表明缓解沉声是阿尔法βT细胞分化的关键.

结论:

负的cis作用元素通过沉默TCRα增强剂起到关键作用,在建立αβT细胞谱系特异性方面发挥关键作用.
沉声剂在实现基因表达的过程中与增强剂同样重要.
区分为αβT细胞血统的区分可能涉及这些沉声器元素的特定减轻.

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