STRUCTURE, CHROMOSOMAL LOCALIZATION, AND METHYLATION PATTERN OF THE HUMAN MB-1 GENE

The Ag receptor on B lymphocytes is a multimeric complex that is compo sed of an Ag-specific component, surface Ig, which is noncovalently as sociated with at least two other proteins, Ig alpha and Ig beta. These are the glycoprotein products of the B lineage-restricted mb-1 and B2 9 genes and are crucial for the cell surface expression and function o f the Ag receptor on B lymphocytes. To better understand the regulatio n of mb-1, we have cloned and sequenced a 5.7-kb genomic DNA fragment that contained the human gene. The overall structure of human mb-1 is very similar to that of the murine gene, including the number and appr oximate size of exons. The promoter region lacks a TATA element, but c ontains two copies of an early B cell factor-binding motif, which prev iously has been shown to be important for murine mb-1 expression. Othe r structural features include two nuclear factor-kappa B binding sites at the 5' end of the gene and a long stretch of AG rich-sequence betw een exons 3 and 4, downstream of an Alu repeat sequence that contains a potential stem-loop structure. The mb-1 gene was localized to chromo some 19q13.2-13.3 by a combination of two methods, PCR amplification o f DNA from a somatic cell hybrid-mapping panel and fluorescence in sit u hybridization. An examination of the methylation pattern revealed a striking correlation between demethylation in the 5' region of the gen e and expression of mb-1 . The demethylated Hpall/Mspl sites are adjac ent to the nuclear factor-kappa B-binding motifs, which suggests a rol e for this transcription factor in the regulation of human mb-1 gene e xpression.