Structure, chromosomal localization, and methylation pattern of the human mb-1 gene.
The Ag receptor on B lymphocytes is a multimeric complex that is composed of an Ag-specific component, surface Ig, which is noncovalently associated with at least two other proteins, Ig alpha and Ig beta. These are the glycoprotein products of the B lineage-restricted mb-1 and B29 genes and are crucial for the cell surface expression and function of the Ag receptor on B lymphocytes. To better understand the regulation 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 approximate size of exons. The promoter region lacks a TATA element, but contains two copies of an early B cell factor-binding motif, which previously has been shown to be important for murine mb-1 expression. Other 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 between exons 3 and 4, downstream of an Alu repeat sequence that contains a potential stem-loop structure. The mb-1 gene was localized to chromosome 19q13.2-13.3 by a combination of two methods, PCR amplification of DNA from a somatic cell hybrid-mapping panel and fluorescence in situ hybridization. An examination of the methylation pattern revealed a striking correlation between demethylation in the 5' region of the gene and expression of mb-1. The demethylated HpaII/MspI sites are adjacent to the nuclear factor-kappa B-binding motifs, which suggests a role for this transcription factor in the regulation of human mb-1 gene expression.
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Department of Microbiology, University of Alabama at Birmingham 35194-3300.
Barnoski
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Sun
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Emanuel
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Burrows
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D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001483:Base Sequence; D051925:CD79 Antigens; D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D004247:DNA / Q000737:chemistry / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005809:Genes, Regulator; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016328:NF-kappa B / Q000235:genetics; D011401:Promoter Regions, Genetic; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014158:Transcription, Genetic
D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; C497882:Cd79a protein, mouse; D017931:DNA Primers; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D004247:DNA