Four conserved promoter motifs regulate transcription of the gene encoding human complement component C2

The early complement components of the classical activation pathway of the complement cascade include the components C1, C4, C2, and C3. These components act in concert to opsonize bacteria, clear immune complexes, and produce inflammatory mediators. They are not structurally homologous nor are they coordinately regulated. The expression of the early complement components is divergent in terms of cytokine responsiveness and tissue specificity. The only pattern of expression shared by the early complement components is inducibility by gamma-IFN and expression in cells of hepatic or monocytic lineage. Nevertheless, four novel conserved promoter motifs were identified in the 5' flanking region of multiple early complement component promoters. Mutation of these four motifs in the C2 promoter decreased transcription in hepatoma cells in transient transfection analyses, and a synthetic promoter consisting of just the four motifs supported transcription in hepatoma cells. Electrophoretic mobility shift assays demonstrate that three of the four conserved elements bind DNA-binding proteins in a tissue-specific manner. One DNA-binding protein is expressed ubiquitously, but the other three are restricted to cells of monocytic or hepatic lineage. Two of the DNA-binding proteins appear to be members of the zinc-finger family of transcription factors. Therefore, these four motifs appear to bind DNA-binding proteins that may function in the tissue-specific expression of C2. Conservation of these four motifs in multiple early complement component genes suggests that these may represent a conserved transcriptional strategy.