FUNCTION AND CONTROL OF OCT-2 EXPRESSION IN T LINEAGE CELLS

B和T细胞发育的调控基因层级 从一个假定的淋巴前体，目前还不清楚。这个 Oct-2基因编码免疫球蛋白基因的发育调节因子 转录，很可能代表调控基因的一个成员 负责B细胞分化的层级。Oct-2蛋白是一种 是POU BOX调节器家族的成员，是一种组织特异性 转录因子。Oct-2在HeLa细胞中的瞬时异位表达 共转染免疫球蛋白启动子激活的结果 建造。骨髓瘤x成纤维细胞杂交瘤细胞的消亡 免疫球蛋白基因表达与Oct-2表达缺失相关。 Oct-2的表达并不局限于B细胞 血统。OCT-2在一些转化的T细胞系中表达。我们有 发现Oct-2基因在静息T细胞中低水平表达 克隆，该基因通过信号转导在T细胞激活时上调 通过T细胞受体。到目前为止，还没有OCT-2的函数 在T血统的细胞中表现出来。这个项目的目标是 探讨Oct-2在发育过程中的作用和调控 T淋巴细胞的成熟。具体目的是：1)分析 OCT-2在T细胞发育和功能成熟过程中的表达； 2)剖析了OCT-2在T细胞中表达的调控机制 细胞激活，包括调控元件的特性 OCT-2基因能够在T细胞中表达并对 3)通过检测确定Oct-2的T细胞靶基因 克隆基因的调控区域以及试图克隆 与特定的光化学交联的DNA片段 4)检测Oct-2在T细胞活化过程中的作用 利用反义CDNA阻断表达或‘功能 分别构建或显性负Oct-2突变体。这 该项目不仅将补充正在进行的关于10月2日在B 淋巴细胞，但将提供一个很好的系统来检查如何 常见组织特异性转录因子在调控中的作用 由两个不同但相关的细胞谱系组成的网络。这样的分析 将提供对控制正常和 淋巴细胞的恶性发展。

Regulatory gene hierarchies underlying the development of B and T cells from a presumptive lymphoid precursor are at present poorly defined. The Oct-2 gene encodes a developmental regulator of immunoglobulin gene transcription, and is likely to represent a member of a regulatory gene hierarchy responsible for B cell differentiation. The Oct-2 protein is a member of the POU box family of regulators and is a tissue specific transcription factor. Transient ectopic expression of Oct-2 in HeLa cell results in the activation of a co-transfected immunoglobulin promoter construct. In myeloma x fibroblast cell hybrids extinction of immunoglobulin gene expression correlates with loss of Oct-2 expression. The expression of Oct-2 is not exclusively restricted to cells of the B lineage. Oct-2 is expressed in some transformed T cell lines. We have found that the Oct-2 gene is expressed at low levels in resting T cell clones and the gene is up-regulated upon T cell activation by signalling through the T cell receptor. To date, no function for Oct-2 has been demonstrated in cells of the T lineage. The goal of this project is to investigate the function and regulation of Oct-2 during the development and maturation of T lymphocytes. The specific aims are to: 1) analyze the expression of Oct-2 during T cell development and functional maturation; 2) dissect the regulatory mechanism controlling Oct-2 expression during T cell activation including the characterization of regulatory elements in the Oct-2 gene that enable expression in T cells and responsiveness to external stimuli; 3) identify T cell target genes for Oct-2 by testing regulatory regions of cloned genes as well as by attempting to clone DNA segments which are specifically photochemically cross-linked with Oct-2 in vivo; 4)test the function of Oct-2 during T cell activation by blocking expression or' function with the use of anti-sense CDNA constructs or dominant negative Oct-2 mutants, respectively. This project will not only complement ongoing studies on Oct-2 in B lymphocytes, but will provide an excellent system for examining how a common tissue specific transcription factor functions in the regulatory networks of two distinct, but related cell lineages. Such an analysis will provide insight into molecular mechanisms controlling the normal and malignant development of lymphocytes.