REGULATION OF EXPRESSION OF MHC CLASS I GENES

MHC I类基因的转录调控是通过基底细胞膜上的 启动子和调控元件，以实现 不同的组织特异性表达水平， 响应细胞外信号而动态调节。类 I基本启动子由三个元件组成：TATAA盒、启动子 (Inr)和一种新的S盒单元。转录因子USF激活 I类转录通过发起人。S盒， TATAA和Inr介导的启动所需的，与两者相互作用 Sp1和单链DNA结合蛋白YB 1分别 激活和抑制启动子。TATAA和Inr的相对用法 元素在不同的细胞类型中变化。其功能基础是 启动子选择性正在研究中。基础转录 I类基因由于负调控而在组织间变化 由一系列位于大约-400和 -1100 bp。主要的组织特异性调节域跨越区域- 700 bp至-800bp，由重叠的增强子和沉默子组成 元素增强子活性存在于所有细胞类型中，而 沉默者活性与I类水平成反比 表达。增强子因子由Oct 1与 一种新型的糖基化氧化还原敏感因子;沉默因子， 也是一种含有ATF 2的复合物。额外的消音器元件有助于 消极的规则。在人类神经细胞中， 表达类I是由于四个不同的消音器的活动 元素除了-700至-800消音器元件外， 元素出现在-400和-500bp之间。这些上游的去除 沉默子不仅导致I类启动子的活性表达 在神经元细胞中，而且还揭示了活性增强剂的存在。 这种功能启动子的抑制提供了一种快速表达的机制。 和神经元细胞中I类的特异性触发， 感染

MHC class I genes are transcriptionally regulated through the basal promoter and regulatory elements in the 5' flanking sequence, to achieve varying tissue-specific levels of expression which are further dynamically modulated in response to extracellular signals. The class I basal promoter consists of three elements: a TATAA box, an initiator (Inr), and a novel S-box element. The transcription factor USF activates class I transcription through the initiator. The S-box, which is required for both TATAA and Inr mediated initiation, interacts with both Sp1 and the single-strand DNA binding protein, YB1, which respectively activate and repress the promoter. The relative usage of TATAA and Inr elements varies among different cell types. The functional basis of this promoter selectivity is under investigation. Basal transcription of class I genes varies among tissues as a result of negative regulation mediated by a series of silencers located between approximately -400 and -1100 bp. The major tissue specific regulatory domain spans the region - 700bp to -800bp, and consists of overlapping enhancer and silencer elements. Enhancer activity is present in all cell types, whereas silencer activity is inversely proportional to the level of class I expresssion. The enhancer factor consists of Oct 1 in association with a novel, glycosylated , redox-sensitive factor; the silencer factor is also a complex, containing ATF2. Additional silencer elements contribute to the negative regulation. In human neuronal cells the failure to express class I is due to the activities of four distinct silencer elements. In addition to the -700 to -800 silencer element, additional elements occur between -400 and -500bp. Removal of these upstream silencers not only results in active expression of the class I promoter in neuronal cells, but also reveals the presence of an active enhancer. This repression of a functional promoter provides a mechanism for rapid and specific triggering of class I in neuronal cells in response to infection.