The goal of this project is to understand the mechanisms by which transcription factors regulate gene expression in cells of the central nervous system (CNS). Two projects which target this objective have been conducted within the past year: The first project involves an investigation of the molecular mechanisms which regulate MHC class I gene expression in virus-infected cells of the CNS. The principle findings are that measles infection of glial cells results in an induction of MHC class I gene expression. However, the expression of these genes are not induced to virus-infected neuronal cells. The differential expression of MHC class I genes in virus- infected neural cells is explained by a differential induction of IFN- beta gene expression in the cells which is mediated by the transcription factor NFkB. The second project involves the rapid cloning and characterization of transcription factors expressed in human brain by a technique that we have termed signature sequencing analysis. This resulted in the isolation of 133 unique human zinc finger cDNAs of which 118 are novel. These cDNA clones have a high degree of homology to zinc finger genes that have been associated with neuronal development and tumorigenesis. One of these cDNA clones is the human form of the Xenopus Pol III basal transcription factor TFIIIA.
