Cockerill P N, Yuen M H, Garrard W T
J Biol Chem. 1987 Apr 15;262(11):5394-7.
We have located presumptive chromosomal loop anchorage elements within the mouse heavy chain immunoglobulin locus. Analysis of 31 kilobases spanning diversity, joining, enhancer, switch, and the mu and delta constant regions reveals that only a single 1-kilobase segment exhibits specific binding to nuclear matrices. It is of particular significance that the transcriptional enhancer element resides within this matrix association region (MAR). Fine structure mapping indicates that binding is mediated by A+T-rich approximately 350-base pair segments that reside on either side of the enhancer. The MAR sequences residing 5' of the enhancer contain topoisomerase II consensus sequences like the MAR located upstream of the kappa light chain gene enhancer. The heavy chain gene MARs, however, exhibit a lower affinity for matrix association compared to the kappa gene MAR. Significantly, the juxtaposition of enhancer elements with MARs appears to be evolutionarily conserved within the immunoglobulin genes, suggesting that MARs may act as positive and/or negative regulators of enhancer function.
我们已经在小鼠重链免疫球蛋白基因座中定位了假定的染色体环锚定元件。对跨越多样性、连接、增强子、转换以及μ和δ恒定区的31千碱基进行分析发现，只有一个1千碱基的片段显示出与核基质的特异性结合。特别重要的是，转录增强子元件位于这个基质关联区域（MAR）内。精细结构图谱表明，结合是由位于增强子两侧的富含A+T的约350碱基对片段介导的。增强子5'端的MAR序列含有与κ轻链基因增强子上游的MAR类似的拓扑异构酶II共有序列。然而，与κ基因MAR相比，重链基因MAR对基质关联的亲和力较低。值得注意的是，增强子元件与MAR的并列在免疫球蛋白基因中似乎在进化上是保守的，这表明MAR可能作为增强子功能的正调控和/或负调控因子。
