期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：1
页码：260-265
DOI：10.1073/pnas.0303738101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Developmentally regulated V(D)J recombination profoundly influences immune repertoires, but the underlying mechanisms are poorly understood. In the endogenous T cell receptor C{gamma}1 cluster, the 3' V{gamma}3 gene (closest to J{gamma}1) rearranges preferentially in the fetal period whereas rearrangement of the 5' V{gamma}2 gene predominates in the adult. Reversing the positions of the V{gamma}2 and V{gamma}3 genes in a genomic transgene resulted in decreased rearrangement of the now 5' V{gamma}3 gene in the fetal thymus and increased rearrangement of the now 3' V{gamma}2 gene. The reversed rearrangement pattern was not accompanied by significant changes in chromatin accessibility of the relocated V{gamma} genes. The results support a model in which the 3' location is the key determinant of rearrangement in the fetus, after which there is a promoter-dependent inactivation of V{gamma}3 rearrangement in favor of V{gamma}2 rearrangement.
