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TCRα/δ基因座处V(D)J重组的发育调控。

Developmental regulation of V(D)J recombination at the TCR alpha/delta locus.

作者信息

Krangel M S, Hernandez-Munain C, Lauzurica P, McMurry M, Roberts J L, Zhong X P

机构信息

Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

Immunol Rev. 1998 Oct;165:131-47. doi: 10.1111/j.1600-065x.1998.tb01236.x.

DOI:10.1111/j.1600-065x.1998.tb01236.x
PMID:9850858
Abstract

The T-cell receptor (TCR) alpha/delta locus includes a large number of V, D, J and C gene segments that are used to produce functional TCR delta and TCR alpha chains expressed by distinct subsets of T lymphocytes. V(D)J recombination events within the locus are regulated as a function of developmental stage and cell lineage during T-lymphocyte differentiation in the thymus. The process of V(D)J recombination is regulated by cis-acting elements that modulate the accessibility of chromosomal substrates to the recombinase. Here we evaluate how the assembly of transcription factor complexes onto enhancers, promoters and other regulatory elements within the TCR alpha/delta locus imparts developmental control to VDJ delta and VJ alpha rearrangement events. Furthermore, we develop the notion that within a complex locus such as the TCR alpha/delta locus, highly localized and region-specific control is likely to require an interplay between positive regulatory elements and blocking or boundary elements that restrict the influence of the positive elements to defined regions of the locus.

摘要

T细胞受体(TCR)α/δ基因座包含大量V、D、J和C基因片段,这些基因片段用于产生由不同T淋巴细胞亚群表达的功能性TCRδ和TCRα链。该基因座内的V(D)J重组事件在胸腺中T淋巴细胞分化过程中作为发育阶段和细胞谱系的函数受到调控。V(D)J重组过程由顺式作用元件调控,这些元件调节染色体底物对重组酶的可及性。在这里,我们评估转录因子复合物在TCRα/δ基因座内的增强子、启动子和其他调控元件上的组装如何赋予VDJδ和VJα重排事件发育控制。此外,我们提出这样一种观点,即在诸如TCRα/δ基因座这样的复杂基因座内,高度局部化和区域特异性的控制可能需要正调控元件与阻断或边界元件之间的相互作用,这些元件将正元件的影响限制在基因座的特定区域。

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