Stein MF, Lang S, Winkler TH, Deinzer A, Erber S, Nettelbeck DM, Naschberger E, Jochmann R, Stürzl M, Slany RK, Werner T, Steinkasserer A, Knippertz I
CD83 is one of the best-known surface marker for fully mature dendritic cells (DCs) and its cell type- and maturation-specific regulation makes the CD83 promoter an interesting tool for the genetic modulation of DCs. To determine the mechanisms regulating this DC- and maturation-specific CD83 expression, ChIP-on-chip-microarray-, biocomputational-, reporter-, EMSA- and ChIP-analyses were performed. These studies led to the identification of a ternary transcriptional activation complex composed of an upstream regulatory element, a minimal promoter and an enhancer which in this arrangement have not been reported for any other gene so far. Notably, these DNA regions contain a complex framework of IRF- and NFkB-transcription factor binding sites mediating their arrangement. Mutation of any of the IRF-binding sites resulted in a significant loss of promoter activity, whereas over-expression of NFkB-transcription factors clearly enhanced transcription. We identified IRF-1, IRF-2, IRF-5, p50, p65 and cRel to be involved in regulating maturation-specific CD83 expression in DCs. Therefore, the characterization of this promoter complex contributes not only to the knowledge on DC-specific gene regulation, but also suggests the involvement of a transcriptional module with binding sites separated into distinct regions in transcriptional activation as well as cell type- and maturation-specific transcriptional targeting of DCs.