title: Ig/EBP-1: a ubiquitously expressed immunoglobulin enhancer binding protein that is similar to C/EBP and heterodimerizes with C/EBP.
abstract: We report the isolation and characterization of cDNA clones that encode a protein with the same DNA binding specificity as the immunoglobulin heavy chain enhancer binding protein E (muEBP-E). We call the gene encoding this protein Ig/EBP-1. A fusion protein encoded by the cDNA binds specifically to muEBP-E-binding sites (E sites) in both the IgH enhancer and the VH1 promoter. Sequence analysis reveals that Ig/EBP-1 is a member of the "basic-zipper" family of DNA-binding proteins that are characterized by basic regions and heptad repeats of leucine residues. Among known family members, Ig/EBP-1 demonstrates highest homology to C/EBP throughout the DNA-binding domain and leucine repeat region. Ig/EBP-1 and C/EBP have highly overlapping binding specificities; both cloned proteins bind to the IgH enhancer and the VH1 promoter E sites, and Ig/EBP-1 binds to previously characterized C/EBP binding sites in the Rous sarcoma virus (RSV) LTR and the murine albumin promoter. Consistent with their homology in the leucine repeat region, Ig/EBP-1 and C/EBP form heterodimers; Ig/EBP-1 is the first member of this family that has been found to heterodimerize with the well-characterized C/EBP. Ig/EBP-1 mRNA is present in all tissues and cell lines examined, although its levels vary almost 20-fold from different sources, with highest levels in early B cells. In tissues where Ig/EBP-1 and C/EBP are both present, heterodimers may be functionally important. The presence of Ig/EBP-1 in fibroblasts and other tissues where C/EBP is not expressed suggests that Ig/EBP-1 may be functionally important for the activity of the RSV enhancer in these cell types. Finally, elevated expression of Ig/EBP-1 in early B cells may explain in part the enhancer-independent activity of VH promoters early in B-cell development.
authors.affiliation: Department of Biological Chemistry, University of California, Los Angeles.
authors.forename: C
authors.initials: C
authors.lastname: Roman
authors.forename: J S
authors.initials: JS
authors.lastname: Platero
authors.forename: J
authors.initials: J
authors.lastname: Shuman
authors.forename: K
authors.initials: K
authors.lastname: Calame
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D022762:CCAAT-Enhancer-Binding Proteins; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016350:Leucine Zippers; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D016328:NF-kappa B; D009687:Nuclear Proteins; D004247:DNA