REGULATION OF THE T CELL-SPECIFIC GENE CD7

T 细胞特异性基因 CD7 的调控

• 批准号: 2077406
• 负责人: Laura E Schanberg
• 金额: $ 8.71万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-15 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2077406
• 关键词: CD antigens; DNA footprinting; T lymphocyte; affinity chromatography; autoimmune disorder; binding proteins; electroporation; gel mobility shift assay; gene expression; gene induction /repression; genetic enhancer element; genetic regulatory element; genetic transcription; genetically modified animals; hematopoiesis; laboratory mouse; molecular cloning; northern blottings; polymerase chain reaction; southern blotting; transcription factor; transfection; virus diseases

Hematopoietic differentiation involves the interaction of genetic events within the cell and biochemical signals in the microenvironment. T lymphocytes derive from multipotent hematopoietic stem cells which migrate from the fetal liver and bone marrow to the thymus. Within the thymus, T cell ontogeny is marked by the sequential appearance of many lineage specific molecules. While the temporal expression of these molecules has been well studied, the molecular mechanisms responsible for the coordinated activation and expression of the genes for these developmental and tissue specific proteins are largely unknown. The human CD7 molecule is one of the earliest markers of the T cell lineage, appearing on multipotent hematopoietic precursors in the fetal liver and bone marrow prior to their migration to the thymus. CD7 continues to be expressed throughout T cell development and is found on 85% of peripheral T cells. The overall goal of these studies is to understand T cell development through the study of the T cell specific gene, CD7. Since CD7 is one of the earliest T lineage specific genes expressed, the activation of this gene may help convey T cell specificity to hematopoietic stem cells. We propose to identify and characterize the cis-acting elements which are responsible for the tissue specific expression of the CD7 gene using both in vivo and in vitro systems. In addition, we will study the possible extinction of CD7 gene expression by negative regulatory elements located upstream of the gene and explore the consequences of retroviral infection on the regulation of the gene. We believe that understanding the transcriptional regulation of the CD7 gene will yield significant knowledge about mechanisms of tissue specificity and the early molecular events associated with T cell lineage determination. Because of the central role of the T cell in modulating the immune response, an understanding of the relationship between normal and abnormal T cell development is crucial to understanding the pathogenesis and etiology of autoimmunity.

造血分化涉及遗传事件的相互作用 以及微环境中的生化信号。 不 淋巴细胞来源于多能造血干细胞， 从胎儿肝脏和骨髓迁移到胸腺。 内 胸腺，T细胞个体发育的标志是顺序出现的许多 谱系特异性分子。 虽然这些的时间表达 分子已经得到了很好的研究，负责的分子机制 这些基因的协调激活和表达 发育和组织特异性蛋白质在很大程度上是未知的。 的 人CD7分子是T细胞谱系的最早标志物之一， 出现在胎儿肝脏中的多能造血前体上， 在它们迁移到胸腺之前的骨髓中。 CD7仍然是 在整个T细胞发育过程中表达，并在85%的外周血淋巴细胞中发现。 T细胞。 这些研究的总体目标是了解T细胞 通过研究T细胞特异性基因CD7的发展。 以来 CD7是最早表达的T细胞系特异性基因之一， 该基因的激活可能有助于将T细胞特异性传递给 造血干细胞 我们建议识别和表征 顺式作用元件负责组织特异性 使用体内和体外系统表达CD7基因。 在 此外，我们还将研究CD7基因表达的可能消失， 位于基因上游的负调控元件，并探索 逆转录病毒感染对基因调控的影响。 我们 我相信，了解CD7基因的转录调控， 将产生关于组织特异性机制的重要知识 与T细胞谱系相关的早期分子事件 保持战略定力 由于T细胞在调节免疫应答中的核心作用， 免疫反应，了解正常的 而异常的T细胞发育对于理解 自身免疫的发病机制和病因。