The mouse BP-1 gene : Structure, chromosomal localization, and regulation of expression by type I interferons and interleukin-7

• Published in: Genomics (San Diego, Calif.) Vol. 33; no. 2; pp. 167 - 176
• Main Authors: JIYANG WANG, WALKER, H, QUN LIN, JENKINS, N, COPELAND, N. G, WATANABE, T, BURROWS, P. D, COOPER, M. D
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier 15-04-1996
• Subjects: Amino Acid Sequence; Aminopeptidases - genetics; Animals; Antigens, Differentiation, B-Lymphocyte - genetics; B-Lymphocytes - enzymology; Base Sequence; Binding Sites; Biological and medical sciences; Cell Line; Chromosome Mapping; Female; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genes. Genome; Glutamyl Aminopeptidase; Hematopoietic Stem Cells; Interferon Type I - metabolism; Interleukin-7 - metabolism; Male; Metalloendopeptidases - genetics; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Promoter Regions, Genetic; Transcription, Genetic; Up-Regulation; Genetic mapping; Membrane protein; Nucleotide sequence; Enzyme; Transcription promoter; Aminopeptidases; Rodentia; Homology; Gene organization; B-Lymphocyte; Chromosome 3; Gene expression; Vertebrata; Regulation(control); Mammalia; Glutamyl aminopeptidase; Mouse; Hydrolases; Chromosome DNA; Proteinases
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1996.0180

The BP-1/6C3 antigen is a homodimeric, phosphorylated type II membrane integral glycoprotein expressed on immature B-lineage cells, bone marrow stromal cells, thymic cortical epithelial cells, endothelial cells, enterocytes, and renal proximal tubular cells. Biochemical and molecular analysis identified BP-1 as glutamyl aminopeptidase, an ectoenzyme that catalyzes the hydrolysis of acidic amino acid residues from the amino termini of regulatory peptides. We have isolated genomic clones that encode the BP-1 gene (gene symbol Enpep). The gene spans more than 110 kb and contains 20 exons. Except for the first and the last exons, it is composed of small exons ranging from 56 to 171 bp that are separated by introns ranging from less than 100 bp to approximately 10 kb. The zinc binding motif HEXXH and the glutamic acid residue 19 amino acids downstream, which also binds zinc, are encoded in exons 5 and 6. Primer extension analysis revealed a common major transcriptional start site in a pre-B cell line, in a bone marrow stromal cell line, and in kidney cells. The promoter region contains a TATA-like element and potential DNA-binding motifs for lymphocyte-specific transcription factors including Ikaros, BSAP, PU.1, and octamer binding proteins, as well as DNA binding motifs for several ubiquitous transcription factors. An interferon responsive element also located in the promoter region appeared to be functional, since type I interferons (IFN-alpha/IFN-beta) upregulated BP-1 expression in pre-B cell lines. A 2.1-kb promoter fragment, when fused to a luciferase reporter gene, was able to drive luciferase expression in pre-B cells, which normally express BP-1, and the Ag8 cells, in which BP-1 expression is extinguished. The BP-1/ Enpep gene was localized to a distal region of mouse chromosome 3 in a region homologous to human chromosome 4q25. Interestingly, while interleukin-7 (IL-7) induced both cell growth and increased BP-1 expression, IFN-alpha/IFN-beta upregulated BP-1 expression but inhibited IL-7 induced proliferation. This finding indicates that the upregulated BP-1 expression can be disassociated from the cell growth signal.