Interaction and functional interference of C/EBP beta with octamer factorsin immunoglobulin gene transcription

The ubiquitous transcription factor C/EBP beta functions as an activator or inhibitor depending on the ratios of three isoforms translated from in-fra me AUG. We have identified C/EBP binding sites in both light and heavy chai n immunoglobulin (Ig) promoters. Of the two C/EBP sites present in the ligh t chain promoter, the upstream site is essential for promoter function. Mut ation of this element drastically decreases promoter activity, despite the presence of an intact octamer element. Both light and heavy chain promoters were activated or inhibited by C/EBP beta isoforms in transfected cells ac cording to the transactivation ability of these isoforms. Endogenous IgM mR NA and protein were repressed by the inhibitory form, C/EBP beta-3, indicat ing a general role of C/EBP beta, in the regulation of Ig genes. We show th at C/EBP beta-3 forms ternary complexes with Oct-1 and Oct-2 on heavy and l ight chain promoters, and also interacts with both octamer-binding proteins in the absence of DNA. This suggests that interference of Oct-1/Oct-2 func tion by C/EBP beta-3 may account for the observed repression. Inhibition by C/EBP beta-3 occurs not only through a C/EBP site, but also through the oc tamer element, as shown by co-transfection experiments with heterologous pr omoter constructs. Thus, C/EBP beta regulates Ig promoter transcription by modulating octamer factor activity.