Our major goal is to analyze the regulatory mechanism of the T-cell-receptor gene through the analysis of DNase I hypersensitive sites. In addition, by comparison of normal and abnormal regulation of the T-cell--receptor gene we may define a mechanism related to the T cell disorder seen in autoimmune mice. The objective can be achieved with the following specific aims: 1. To analyze DNase I hypersensitive sites in the T-cell-receptor alpha, beta, and gamma chain in the mouse. The DNase I hypersensitive sites will be sequenced and compared with each other and to the immunoglobulin DNase I hypersensitive sites. 2. To evaluate developmental changes of DNase I hypersensitive sites which accompany T cell development. Using cell lines, tumor cells, and hybridomas the relationship between DNase I hypersensitive site and expression / rearrangement will be studied. 3. To define nuclear proteins binding to DNA near DNase I hypersensitive sites of the T-cell receptor gene. We will study whether DNA binding protein exists for the beta chain J-C introns. 4. To study T-cell-receptor disorders in autoimmune mice to help understand certain aspects of the process. We have recently observed a disorder of rearrangement and expression in T-cell-receptor genes in autoimmune mice. We will study the genetic disorder mechanism involving T-cell-receptor gene by investigating the DNase I hypersensitive sites and the DNA binding proteins.
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| Hashimoto, Y (1989) T cell receptor beta gene has two downstream DNase I hypersensitive regions. Possible mechanisms of tissue- and stage-specific gene regulation. J Exp Med 169:2097-107 |
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| Yui, K; Hashimoto, Y; Wadsworth, S et al. (1987) Characterization of Lyt-2-, L3T4- class I-specific cytolytic clones in C3H-gld/gld mice. Implications for functions of accessory molecules and programmed development. J Exp Med 166:1026-40 |
