DIFFERENTIATION-SPECIFIC, OCTAMER-DEPENDENT COSTIMULATION OF KAPPA TRANSCRIPTION

By mutational analysis of the octamer-TATA box intervening region in t he mouse SP6 kappa promoter, we have mapped two octamer-dependent, cos timulatory regions, A and B, The A region was active in late B cells o nly, while the B region was active throughout B cell differentiation, The B region was TATA proximal and contained a heptamer and an E box o f the E2A type that is common in VK promoters, Mutation of the heptame r element did not decrease transcriptional stimulation from this regio n, but mutations in, or immediately 5' of, the E box core sequence did , A protein binding to this region could be detected in nuclear extrac ts, The complex: could only partially be competed with a mu E5 binding site and could not be supershifted with Abs raised to E2A gene produc ts, indicating that it may represent a novel E-box binding complex, Th e A region was located proximal to the octamer and contained a CCCT el ement that is conserved both with regard to position and sequence in h uman V kappa II promoters, By mutational analysis, the transcriptional stimulatory activity was mapped to the CCCT element that also is part of an early B cell factor (EBF) binding site, in late B cells, a nove l protein (FA), which did not bind to the EBF binding site in the mb1 promoter, interacted with the A region, This protein was found to be e xpressed at lower levels in early B cells as well as in HeLa tells, Th us, the octamer-flanking sequence contains positive control elements t hat may act independently but that differ in the stage of B cell diffe rentiation at which they are active, One of these factors is an exampl e of an ubiquitously expressed transcription factor that participate i n differentiation-specific transcriptional activation.