IDENTIFICATION OF NOVEL UBIQUITOUS AND CELL-TYPE-SPECIFIC FACTORS THAT SPECIFICALLY RECOGNIZE IMMUNOGLOBULIN HEAVY-CHAIN AND KAPPA-LIGHT-CHAIN PROMOTERS

In a search for novel factors that interact with the octamer element, immunoglobulin kappa light chain (V-kappa) and heavy chain (V-H) gene promoters were compared for binding to nuclear proteins from lymphoid cells. Both promoters showed a similar pattern of bound factors, which was entirely different from that seen with the human immunodeficiency virus, type I promoter. Besides OTF-1 (Oct-1) and OTF-2 (Oct-2), at l east three additional complexes were observed. Two of these were funct ionally analyzed: C1, a slowly migrating complex, which was much more abundant in B cells than in non-lymphoid cells, and C4, which appeared to have ubiquitous distribution. As determined by several methods, th e protein(s) forming the C1 complex bound on the V-kappa gene to a sit e that partially covers the octamer element, whereas, surprisingly, in the V-H gene a region spanning the TATA box up to the transcriptional initiation site was recognized. The ubiquitous C4 complex was analyze d for the light chain promoter. The protein specifically bound to a si te immediately 5' to the octamer. By in vitro transcription analysis, we found that C4 augments the octamer-dependent transcription of the V -kappa gene. The activation required binding of OTF-1/OTF-2, and C4 co uld not stimulate transcription by itself, implying a synergistic inte raction. Due to the overlapping binding sites, the effect of C1 by its elf could not be clearly separated from the C4 effect. However, the sp ecific interaction of C1 with crucial control elements of light chain and heavy chain promoters strongly suggests a functional role in immun oglobulin gene transcription control.