Isolation and characterization of the human DC-SIGN and DC-SIGNR promoters

DC-SIGN is a C-type lectin expressed on the surface of dendritic cells (DCs) that is used by a number of human pathogens to disseminate infection in the host. In the human genome, there is a gene closely related to DC-SIGN, termed DC-SIGNR (also L-SIGN, DC-SIGN2), which likely arose through gene duplication. DC-SIGN protein and RNA expression is largely restricted to DCs and some specialized macrophages in lung and placenta, while DC-SIGNR expression is largely restricted to lymph nodes and liver sinusoidal endothelial cells. To begin to investigate the cell type-restricted expression of these closely related genes, we isolated the human DC-SIGN and DC-SIGNR promoters. They were found to be relatively weak promoters that express similarly in plasmid transfection assays in several transformed cell lines, suggesting that the cis-regulatory elements that confer cell-type restricted expression of these two genes are located outside of the promoters. The DC-SIGN gene contains four major transcriptional start sites at + 1, + 271, + 364, and + 435, with the + 364 site being the most abundantly expressed in DCs. The DC-SIGN promoter is contained within nucleotides + 251 to + 487. AP-1, Sp1, Ets-1, and NF-KB binding sites in the DC-SIGN promoter appear to be important for function. Thus, despite its highly restricted pattern of expression, the DC-SIGN promoter has features common to promoters that are active in other cell types. (C) 2003 Elsevier Science B.V. All rights reserved.