Mather E L, Perry R P
Proc Natl Acad Sci U S A. 1983 Aug;80(15):4689-93. doi: 10.1073/pnas.80.15.4689.
Immunoglobulin V kappa genes are transcriptionally silent in their germline context and become transcriptionally active upon fusion to the J kappa-C kappa region (kappa locus). To elucidate the role of chromosomal structure in this regulatory phenomenon we have investigated the DNase I sensitivity and methylation status of the kappa locus and selected V kappa genes in a variety of alleles exhibiting different rearrangement configurations and different levels of transcriptional activity. Our findings indicate that the kappa locus in either germline or rearranged contexts maintains a distinctive DNase I-sensitive, hypomethylated structure in plasmacytomas and hybridomas, irrespective of its level of transcriptional activity. In contrast, the germline V kappa genes are in less accessible regions of chromatin and more highly methylated regions of DNA. Upon fusion to the kappa locus, V kappa genes become DNase I-sensitive and hypomethylated. This effect extends several kilobases upstream of the transcriptional initiation site but does not extend to the adjacent V kappa gene or to the identical V kappa allele on the other chromosome, indicating that the structural alteration is a localized cis-acting phenomenon.
免疫球蛋白Vκ基因在其种系背景下转录沉默，而在与Jκ-Cκ区域（κ基因座）融合后变得转录活跃。为了阐明染色体结构在这种调控现象中的作用，我们研究了κ基因座以及在多种呈现不同重排构型和不同转录活性水平的等位基因中选定的Vκ基因的DNA酶I敏感性和甲基化状态。我们的研究结果表明，无论转录活性水平如何，种系或重排背景下的κ基因座在浆细胞瘤和杂交瘤中均维持一种独特的对DNA酶I敏感、低甲基化的结构。相比之下，种系Vκ基因处于染色质较难接近的区域以及DNA甲基化程度较高的区域。与κ基因座融合后，Vκ基因变得对DNA酶I敏感且低甲基化。这种效应延伸至转录起始位点上游数千碱基，但并不延伸至相邻的Vκ基因或另一染色体上相同的Vκ等位基因，这表明结构改变是一种局部的顺式作用现象。
