Gene rearrangement patterning and DNase-I hypersensitive sites within the T-cell receptor J alpha locus.

Gene rearrangement patterning and DNase-I hypersensitive sites within the T-cell receptor J alpha locus.
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T 细胞受体 J α 基因座内的基因重排模式和 DNase-I 超敏感位点。

DOI:
10.1016/0161-5890(95)00021-6
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发表时间:
1995
影响因子:
3.6
通讯作者:
Hurwitz,JL
Hurwitz,JL
中科院分区:
医学3区
文献类型:
--
作者:
Dave,VP;Hurwitz,JL

文献摘要

被引文献

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多年来,αβ 和 γδ T 细胞祖细胞之间的关系一直是争论的话题。一些人认为,T 细胞祖细胞的一个子集“预先定型”为 αβ 谱系,因此被编程为重新排列 α 基因,而不是 δ 基因。进一步认为,通过独特的重排 δrec-ΨJα 删除 δ 位点可能是 αβ 定型细胞中 V-Jα 连接的关键先行者,并且称为 5'TEA 的超敏感位点 (HS) 可能调节这种重排。在这里我们提出一个替代假设。我们首先强调,定向 Jα 基因重排并不专门针对 ΨJα 基因,而是在 T 细胞发育过程中整个 Jα 基因座发生簇状基因重排。我们描述了沿 Jα 基因座分布的不是一个而是至少两个 HS 位点的存在,这些位点可能充当基因重排事件的调节因子。最后,我们认为祖T细胞并不致力于特定的δ或α基因重排,而是灵活的祖细胞对环境信号和散布在δα基因中的多个调节元件之间的复杂相互作用做出反应。
For several years, the relationship between αβ and γδ T-cell progenitors has been a topic of debate. Some argue that a subset of T-cell progenitors is “pre-committed” to the αβ lineage and is thus programmed to rearrange α, but not δ genes. It is further argued that the deletion of the δ locus by a unique rearrangement, δrec-ΨJα, may be the critical forerunner to V-Jα joins in αβ committed cells and that a hypersensitive site (HS) termed 5'TEA might regulate such rearrangement. Here we present an alternative hypothesis. We first emphasize that directed Jα gene rearrangements do not exclusively target the ΨJα gene, but that clustered gene rearrangements occur throughout the Jα locus during T-cell development. We describe the existence of not one, but at least two HS sites distributed along the Jα locus which might serve as regulators for the gene rearrangement event. Finally, we suggest that progenitor T-cells are not committed to a particular δ or α gene rearrangement, but that a flexible progenitor responds to complex interactions between environmental signals and multiple regulatory elements interspersed among δ α genes.