DIFFERENTIAL TRANSACTIVATION POTENTIAL OF OCT1 AND OCT2 IS DETERMINED BY ADDITIONAL B-CELL-SPECIFIC ACTIVITIES

Cell type-specific transcriptional regulation is generally believed to be mediated by sequence-specific transcription factors that are specifically present in the corresponding cells. The interaction of the lymphoid-specific Oct2 transcription factor has been thought to be responsible for the B cell-specific activity of octamer-containing promoter and enhancer elements. Here we show that physiological concentrations of Oct2 do not suffice to generate octamer-dependent promoter activity in non-B cell lines. Furthermore, we have tested the activity of octamer-dependent promoter and enhancer elements in B cell lines that lack the endogenous Oct2 protein. Our results demonstrate that in these Oct2-deficient B cells the ubiquitous endogenous Oct1 protein is able to stimulate octamer-containing promoters to a level comparable with that of normal Oct2-positive B cells. However, reporter constructs bearing the octamer motif in a distal enhancer position are not stimulated by the Oct1 protein, but do require the presence of Oct2. The B cell-specific octamer-dependent promoter activity mediated by Oct1 correlates with the presence of a novel B cell-specific octamer-binding complex containing the Oct1 protein. From these results we conclude that B cells contain two different activities: one that interacts with both Oct1 and Oct2 and mediates promoter proximal activity of the octamer motif and a second that specifically interacts with Oct2 to confer function from a remote enhancer position.