REGULATION OF EXPRESSION OF MHC CLASS I GENES

编码移植抗原的MHC-I类基因普遍存在 表达，尽管它们的表达水平在不同的组织中不同。 猪I类基因5‘侧翼DNA序列分析 证明了这一区域包含了一系列消极和积极的 监管要素。这些元素之一，由重叠部分组成 消极和积极的监管要素，是一个监管领域 负责建立MHC-I类基因的组织特异性水平 表情。一系列嵌套式转基因小鼠的导入 在调节结构域的范围上不同的缺失突变体， 显示增强子活性主要存在于淋巴组织中。这个 组织特异性结构域形成不同的增强子和抑制子相关 具有细胞反式作用因子的复合体。增强子结合活性 存在于各种细胞类型的提取液中，与 第I类表达。相比之下，消音器绑定的级别为 与I类基因表达水平成反比。因此， I类基因被发现是负调控的。生化 对调控因素的表征表明，每个因素 因子至少由两个不同的组件组成，其中一个组件显示 这两个因素都是共同的。消音器和增强器因素都是 对氧化还原反应敏感。增强因子复合体的大小约为3okD。这个 增强子独特的亚基也是糖基化的。消音器因子复合体 约为95kD。 已经确定了另一个负面监管元素，即 原癌基因c-jun以同源或异源二聚体的形式结合，并作为 特定的负调节器。这些观察结果。建议我上一班 在细胞激活过程中，表达受到积极的调节，也提示 C-jun癌基因变体转化的细胞可以 减少I类基因的表达。

MHC class I genes encoding transplantation antigens are ubiquitously expressed, although their level of expression varies among tissues. Analysis of the 5' flanking DNA sequence of a swine class I gene has demonstrated that this region contains a series of negative and positive regulatory elements. One of these elements, consisting of overlapping negative and positive regulatory elements, is a regulatory domain responsible for establishing tissue-specific levels of MHC class I gene expression. Introduction into transgenic mice of a series of nested deletion mutants which differ in the extent of the regulatory domain, reveals that the enhancer activity predominates in lymphoid tissues. The tissue-specific domain forms distinct enhancer and silencer associated complexes with cellular trans acting factors. Enhancer binding activity is present in extracts from various cell types, independent of levels of class I expression. In contrast, the level of silencer binding is inversely proportional to the level of class I gene expression. Thus, class I genes are found to be negatively regulated. Biochemical characterization of the regulatory factors has demonstrated that each factor consists of at least two distinct components, one of which appears to be common to both factors. Both the silencer and enhancer factors are redox-sensitive. The enhancer factor complex is approximately 3OkD. The enhancer unique subunit is also glycosylated. The silencer factor complex is approximately 95kD. An additional negative regulatory element has been identified which the proto-oncogene, c-jun, binds as a homo or heterodimer, and acts as a specific negative regulator. These observations. suggest that class I expression is actively regulated during cell activation, and also suggest a mechanism whereby cells transformed by oncogenic variants of c-jun could decrease class I expression.