THE REGULATORY GENE, HXBP-1, AND ITS TARGET, HLA-DRA, UTILIZE BOTH COMMON AND DISTINCT REGULATORY ELEMENTS AND PROTEIN COMPLEXES

hXBP-1 is a transcription factor of the leucine zipper (b-zip) family important in the expression of the class II major histocompatibility c omplex gene, DRA. Studies with mouse-human hybrids have mapped hXBP-1 hybridizing fragments to human chromosomes 5 and 22 and the frequent d etection of two mRNA transcripts suggested that hXBP-1 may be a member of a small gene family. To analyze the structure and regulation of hX BP-1 further, cosmid clones from both chromosomes were isolated. Mappi ng and sequence analyses reveal that chromosome 22 contains the functi onal hXBP-1 gene while chromosome 5 contains a processed pseudogene. h XBP-1 promoter analysis has revealed that cis-active elements within t he 5'-untranslated region of hXBP-1 are essential for full promoter ac tivity. One such element, hX2, is identical to the hXBP-1 target seque nce in the DRA promoter. Mutagenesis of the hX2 site substantially dec reases promoter activity. This element interacts with four distinct pr otein complexes in mature B cells and cross-competition experiments sh ow that two of these complexes (complex 1 and complex 4) also interact with the hXBP-1 target sequence (X2) from the DRA promoter. The simil arities of the hXBP-1 promoter and of the DRA promoter (the gene that the hXBP-1 protein regulates) are further emphasized by the fact that a Y box element is located 3' of both hX2 and X2.