Characterization of the CD83 promoter/enhancer complex

CD83 is one of the best-known surface markers for mature dendritic cells (DC). As CD83 is specifically upregulated upon DC maturation, a highly cell type- and maturation status-specific gene regulation is hypothesized. To elucidate the regulation mechanisms of CD83 expression in human DC, ChIP-chip-microarray-, biocomputational-, reporter, CpG-methylation- and EMSA -analyses were performed. By these studies, a tripartite transcriptional activation complex composed of an upstream regulatory element, a minimal promoter and an enhancer was identified. Their specific arrangement and cooperation in trans, mediated by a complex framework of IRF- and NFkB-binding sites, has not been reported for any other gene so far. The characterization of the CD83 promoter complex not only allows a detailed look into the elaborate mechanisms of the immune response in general and the biology of DC in particular, but also exemplarily unfolds the cooperation of various promoter elements in a highly cell type- and status-specific immune cell related promoter. Thus, for the first time, a human mature DC-specific promoter is described that might become an important tool for transcriptional targeting of DC.

Autorentext

was born in 1980. He studied Biology at the FAU Erlangen-Nürnberg and acquired his PhD in the fields of genetics and immunology. Currently M. Stein is employed as researcher at the Universitätsklinikum Erlangen, Dept. of Immune Modulation and investigates the function and regulation of surface marker CD83 in dendritic cells and regulatory T cells.