An inducible enhancer controls the expression of the human interleukin 1 beta gene

This paper describes regulatory sequences responsible for the control of human interleukin 1 beta gene expression in cells of the monocytic lineage. Hybrid plasmids containing different regions of the interleukin 1 beta gene and the bacterial chloramphenicol acetyltransferase gene were transfected into human monocytic THP-1 or U937 cells. After treatment with 12-O-tetradecanoylphorbol-13-acetate, which triggers cell differentiation, we have identified an enhancer sequence which mediates the induction of gene activity by 12-O-tetradecanoylphorbol-13-acetate. The enhancer, approximately 180 base pairs long, is located between positions -2982 and -2795 upstream from the transcriptional start site. Further analysis has shown that 132 base pairs immediately upstream from the start site of transcription are sufficient to promote constitutive expression of the gene. Additional promoter elements, located within the first intron, maximize the level of gene expression. Although activated monocytes and macrophages are the main producers of interleukin 1 beta, both the enhancer and the constitutive promoter can function in monocytic cells as well as in nonmonocytic HeLa cells.