Molecular principles of Oct2-mediated gene activation in B cells

Abstract

The octamer motif is a crucial regulatory element for immunoglobulin promoter and enhancer function. We have investigated the molecular mechanisms that underlie octamer-mediated gene activation in B cells. This B cell-specific transcriptional regulation is subject to a novel type of regulatory mechanism. We could demonstrate that octamer-dependent transcription is not only regulated by specific DNA-binding transcription factors, but in addition requires the activity of B cell-restricted cofactors. Both octamer-dependent promoter and enhancer activation depend on such a combination of transcription factor and cofactors. However, the exact requirements differ for these two situations. Promoter activity can be achieved with either one of two distinct transcription factors, Oct1 and/or Oct2, together with the cofactor OCA-B1. In contrast, only Oct2 in conjunction with an additional cofactor, OCA-B2, can confer enhancer activity.