NOVEL POU PROTEIN AND LYMPHOCYTE GENE EXPRESSION

解开调节淋巴系统的潜在分子机制 表型和淋巴样成熟对于我们理解 免疫功能。POU结构域蛋白被发现是关键的 发育和维持特定谱系的成熟表型。 POU蛋白通过调控谱系特异性基因影响发育 通过八聚体或与八聚体相关的基序表达。猪的突变 基因影响这种相互作用，并导致发育异常。 特定的血统。八聚体和类似八聚体基序在生物信息学中的重要性 淋巴细胞特异性基因的表达已有很好的文献记载。已知的淋巴组织 POU蛋白不能令人满意地解释大多数八聚体依赖 淋巴组织特异性基因表达。 我们已经鉴定出一种新的淋巴POU蛋白，TCFbeta1，它是 与其他已知POU蛋白有较远的亲缘关系。我们建议在这里做实验。 旨在揭示其在成熟淋巴细胞和T细胞中的功能 发展。这将涉及确定废除下列条款的效果 TCFbeta1活性对淋巴表型的影响。具体来说，研究是 描述了它在调节钙敏感中的作用 IL-2基因表达中的信号通路。 我们还将参与消除小鼠胸腺中TCFbeta1的活性 转基因小鼠为了解TCFbeta1在T细胞中的作用 发展。他们将阐明三个不同角色的比较作用 T细胞发育中的淋巴POU结构域蛋白。 这些研究将有助于产生组织培养和小鼠免疫模型 有助于阐明淋巴细胞发育和功能的功能障碍。

Unraveling the underlying molecular mechanisms which regulate the lymphoid phenotype and lymphoid maturation is crucial for our understanding of immune function. POU domain proteins have been found to be critical for development and maintenance of the mature phenotype of specific lineages. POU proteins affect development be regulating lineage specific gene expression via athe octamer or octamer related motifs. Mutation of POU genes affects this interaction and leads to aberrations in development of specific lineages. The importance of octamer and octamer like motifs in lymphocyte specific gene expression is well documented. The known lymphoid POU proteins can not satisfactorily explain most of the octamer dependent lymphoid specific gene expression. We have identified a novel lymphoid POU protein, TCFbeta1 which is distantly related to other known POU proteins. We propose here experiments designed to reveal its function in mature lymphoid cells and during T cell development. This will involve determining the effect of abrogation of TCFbeta1 activity on the lymphoid phenotype. In particular studies are described which address its role in regulating the Calcium sensitive signaling pathway in Il2 gene expression. We will also be involved with abrogate TCFbeta1 activity in thymus of transgenic mice in order to understand athe role of TCFbeta1 in T cell development. They will clarify the comparative roles of three different lymphoid POU domain proteins in T cell development. These studies will help generate tissue culture and mouse models of immune dysfunction which help in elucidating lymphocyte development and function.