Promoter analysis of interleukin 19

Interleukin (IL)-19 belongs to the IL-10 family which includes IL-19, IL-20, IL-22, AK155, and MDA-7. IL-10 is a potent immunomodulatory cytokine with implications for pathogenesis in various autoimmune diseases. Polymorphism of the IL-10 promoter region correlates with disease outcome. To understand the gene regulation of IL-19, we analyzed the IL-19 promoter region. A regulatory region (PE), 148 bp upstream of exon 1 of IL-19 and linked to a luciferase reporter gene, supported luciferase activity 13 times greater than that supported by a negative promoterless control. An electrophoretic mobility shift assay (EMSA) showed specific binding sites for the transcription factors of the oligonucleotides PE1 (−148 to −98) derived from PE. We identified the sequence TGTGGT (−142 to −138) on PE1 as the binding site for the transcription factor AML1, and crucial for the promoter activity of IL-19 because substituting 1 bp in the PE region (−139G → T) abolished IL-19 promoter activity.