A role for histone acetylation in the developmental regulation of V(D)J recombination
A role for histone acetylation in the developmental regulation of V(D)J recombination
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DOI：
10.1126/science.287.5452.495
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发表时间：
2000-01-21
期刊：
影响因子：
56.9
通讯作者：
Krangel, MS
中科院分区：
文献类型：
--
作者：
McMurry, MT;Krangel, MS
V（D）J重组在体内通过染色体重组信号序列对重组酶的可及性的增强子依赖性变化而发育调节，但这些变化的分子性质是未知的。在此，沿转基因V（D）J重组报告基因和内源性T细胞受体α/δ基因座的沿着形式测量组蛋白H3乙酰化。增强子活性显示出赋予H3乙酰化中的tong-range、发育调节的变化，并且H3乙酰化状态与V（D）J重组紧密相关。H3超乙酰化被认为是V（D）J重组的增强子活性与可接近性的分子机制，V（D）J重组在体内受染色体重组信号序列对重组酶的可接近性的增强子依赖性变化的发育调控，但这些变化的分子本质尚不清楚。在此，沿转基因V（D）J重组报告基因和内源性T细胞受体α/δ基因座的沿着形式测量组蛋白H3乙酰化。增强子活性显示出在H3乙酰化中赋予长范围的、发育调节的变化，并且H3乙酰化状态与V（D）J重组紧密相关。H3超乙酰化被认为是一种将增强子活性与V（D）J重组的可及性相结合的分子机制。
V(D)J recombination is developmentally regulated in vivo by enhancer -dependent changes in the accessibility of chromosomal recombination signal sequences to the recombinase, but the molecular nature of these changes is unknown. Here histone H3 acetylation was measured along versions of a transgenic V(D)J recombination reporter and the endogenous T cell receptor alpha/delta locus. Enhancer activity was shown to impart tong-range, developmentally regulated changes in H3 acetylation, and H3 acetylation status was tightly linked to V(D)J recombination. H3 hyperacetylation is proposed as a molecular mechanism coupling enhancer activity to accessibiLity for V(D)J recombination.V(D)J recombination is developmentally regulated in vivo by enhancer-dependent changes in the accessibility of chromosomal recombination signal sequences to the recombinase, but the molecular nature of these changes is unknown. Here histone H3 acetylation was measured along versions of a transgenic V(D)J recombination reporter and the endogenous T cell receptor alpha/delta Locus. Enhancer activity was shown to impart Long-range, developmentally regulated changes in H3 acetylation, and H3 acetylation status was tightly Linked to V(D)J recombination. H3 hyperacetylation is proposed as a molecular mechanism coupling enhancer activity to accessibility for V(D)J recombination.