The original goals of this project concerned the expression of anti-arsonate hybridomas. In particular, we hoped to understand something of the germline contribution to the anti-arsonate immune response. These goals have been largely met. During the past five years, this grant also funded work concerning transcription initiation through the VH-promoter-associated octamer motif. The VH genes of the arsonate system as well as other murine VH and VL genes were used to gain insight into the factors that regulated immunoglobulin gene expression. The present application is wholly directed toward this latter issue and is divided into three aims: First, we seek to continue our studies on the """"""""conventional"""""""" ubiquitous octamer binding protein, OTF1, which promotes B-cell stage-specific transcription in lieu of OTF2.
Aims 2 and 3 focus on two types of """"""""unconventional"""""""" octamer-binding proteins (i.e., lack the prototypic POU domain of OTF1, OTF2 and related factors). One of these, P3, represents a new class of DNA-binding proteins and shares striking homology with a Drosophila protein involved in visual processing. The other is the well-known Ku antigen, a DNA-associated nuclear protein recognized by sera from patients with certain autoimmune diseases. We propose studies of both a molecular biological as well as a biochemical nature that should provide insight into the mechanisms of promoter region function in the murine immune and nervous systems.
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