NOVEL POU PROTEIN AND LYMPHOCYTE GENE EXPRESSION

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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.