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-kappaB 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.
Liu
Hongbing
H
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Yu
Wendong
W
Liou
Li Ying
LY
Rice
Andrew P
AP
D001483:Base Sequence; D015152:Blotting, Northern; D015815:Cell Adhesion Molecules / Q000235:genetics*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D037181:Lectins, C-Type / Q000235:genetics*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D024363:Transcription Initiation Site; D014162:Transfection; D014407:Tumor Cells, Cultured; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D004247:DNA; D037181:Lectins, C-Type; D008156:Luciferases; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C433029:CLEC4M protein, human