REGULATION OF THE T CELL-SPECIFIC GENE CD7

T 细胞特异性基因 CD7 的调控

• 批准号: 3079366
• 负责人: Laura E Schanberg
• 金额: $ 8.81万
• 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/3079366
• 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 细胞内和微环境中的生化信号。 时间 淋巴细胞来源于多能造血干细胞， 从胎儿肝脏和骨髓迁移至胸腺。 内 在胸腺中，T 细胞个体发育的特点是许多细胞的连续出现 谱系特异性分子。 虽然这些的时间表达 分子已被充分研究，其分子机制 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。 这 人类CD7分子是T细胞谱系最早的标记之一， 出现在胎儿肝脏中的多能造血前体细胞上， 骨髓在迁移到胸腺之前。 CD7 继续 在 T 细胞发育过程中表达，存在于 85% 的外周细胞中 T细胞。 这些研究的总体目标是了解 T 细胞 通过研究 T 细胞特定基因 CD7 进行开发。 自从 CD7是最早表达的T谱系特异性基因之一 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。 我们建议识别并描述 负责组织特异性的顺式作用元件 使用体内和体外系统表达 CD7 基因。 在 此外，我们将通过以下方式研究 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节的影响。 我们 相信了解CD7基因的转录调控 将产生有关组织特异性机制的重要知识 以及与 T 细胞谱系相关的早期分子事件 决心。 由于 T 细胞在调节中起核心作用 免疫反应，了解正常之间的关系 异常的 T 细胞发育对于理解 自身免疫的发病机制和病因学。