Control of V(D)J recombinational accessibility of the Dβ1 gene segment at the TCRβ locus by a germline promoter
Control of V(D)J recombinational accessibility of the Dβ1 gene segment at the TCRβ locus by a germline promoter
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DOI：
10.1016/s1074-7613(00)80031-x
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发表时间：
1999-03-01
期刊：
影响因子：
32.4
通讯作者：
Chen, JZ
中科院分区：
文献类型：
--
作者：
Whitehurst, CE;Chattopadhyay, S;Chen, JZ
缺失小鼠TCRβ基因Dβ1基因上游的胚系启动子区域，以评价其在控制V(D)J重组中的作用。随着Dβ1区生殖系转录的减少，Dβ1而不是Dβ2基因片段的重排减少了10-20倍。只有当分析纯化的CD4(-)CD8(-)胸腺细胞时，RAG介导的Dβ1和Jβ1信号序列的裂解才明显减少，因为正如我们所证明的，这些基因片段的裂解也发生在CD4(+)CD8(+)胸腺细胞中。这些发现表明，生殖系启动子调节重组基因片段的局部可及性，而在CD4(+)CD8(+)胸腺细胞中，TCRβ等位基因排斥并不是由于Dβ基因片段不可及而导致的。
The germline promoter region upstream of the D beta 1 gene segment in the murine TCR beta locus was deleted to assess its role in controlling V(D)J recombination. Associated with diminished D beta 1 region germline transcription, rearrangement of the D beta 1 but not the D beta 2 gene segment was reduced 10- to 20-fold. A corresponding reduction in RAG-mediated cleavage at the D beta 1 and J beta 1 signal sequences was apparent only when purified CD4(-)CD8(-) thymocytes were analyzed because, as we demonstrate, cleavage at these gene segments also occurred in CD4(+)CD8(+) thymocytes. These findings suggest that germline promoters regulate localized accessibility of gene segments for recombination and that in CD4(+)CD8(+) thymocytes TCR beta allelic exclusion does not result from inaccessibility of D beta gene segments.