REGULATION OF EXPRESSION OF CLASS I MHC GENE

编码移植抗原的MHC I类基因是普遍存在的， 表达，尽管它们的表达水平在组织中不同。 猪I类基因5'侧翼DNA序列的分析 证明除了典型的启动子之外，该区域 包含一系列的负调控和正调控元件。 之一 与该基因相关的调控元件（RE-140）由以下组成： 积极和消极的元素。 转基因导入 小鼠的一系列巢式缺失含有一个共同的3'末端，但 5'侧翼调控序列的程度不同，揭示了 这种复杂的调节元件以组织特异性方式起作用， 使得增强子活性在淋巴组织中占优势，但不 在非淋巴组织中。 另一个负调控元件RE-105， 已鉴定出与RE-140在序列和 功能 在转基因动物中，RE 105在所有基因组中都起到沉默者的作用。 检查组织。 RE-140的消声器组件已被证明具有显著的 与酵母交配型阻遏系统相似。 一个中等的DNA 在酵母和哺乳动物操纵基因之间存在序列同源性。 哺乳动物因子与酵母α 2操纵子结合，并且还特异性地 与酵母α 2结合蛋白相互作用。 此外，酵母α 2 操纵子在哺乳动物细胞中起着沉默元件的作用， 在MHC I类启动子的上游。 所有功能上鉴定的调节元件都是 与反式作用因子有关。 RE-140 DNA形成不同的增强子 和与细胞因子相关的沉默子复合物。 每个由 至少有两个不同的因素。 分析来自一个 多种细胞系和组织显示RE-140增强子结合 活性存在于所有提取物中，与I类水平无关 表情 RE-140沉默子结合活性的水平是相反的。 与I类基因表达水平成比例。 这些研究 导致I类基因被负调控的提议。

MHC class I genes encoding transplantation antigens are ubiquitously expressed, although their level of expression varies among tissues. Analysis of the 5' flanking DNA sequences of a swine class I gene has demonstrated that in addition to the canonical promoter, this region contains a series of negative and positive regulatory elements. One of the regulatory elements (RE-140) associated with this gene consists of overlapping negative and positive elements. Introduction into transgenic mice of a series of nested deletions containing a common 3' terminus, but differing in the extent of 5' flanking regulatory sequences, reveals that this complex regulatory element functions in a tissue specific manner, such that the enhancer activity predominates in lymphoid tissues, but not in non-lymphoid tissues. Another negative regulatory element, RE-105, has been identified which is distinct from RE-140 in both sequence and function. In transgenic animals, RE105 functions as a silencer in all tissues examined. The silencer component of RE-140 has been shown to have striking similarities to the yeast mating type repression system. A moderate DNA sequence homology exists between the yeast and mammalian operators. Mammalian factors bind to the yeast alpha2 operator and also specifically interact with a yeast alpha2-binding protein. Further, the yeast alpha2 operator functions as a silencer element in mammalian cells when placed upstream of a MHC class I promoter. All of the functionally identified regulatory elements are associated with trans acting factors. RE-140 DNA forms distinct enhancer and silencer associated complexes with cellular factors. Each consists of at least two distinct factors. Analysis of binding activity from a variety of cell lines and tissues reveals that RE-140 enhancer binding activity is present in all extracts, independent of the level of class I expression. The level of RE-140 silencer binding activity is inversely proportion to the level of class I gene expression. These studies have led to the proposal that class I genes are negatively regulated.