IDENTIFICATION OF AN AP-2 ELEMENT IN THE -323-REGION TO -285-REGION OF THE TNF-ALPHA GENE

We have identified a region of the human TNF-alpha promoter between nu cleotides -323 and -285, capable of influencing transcriptional activi ty. This region encompasses the -308 polymorphism and contains a 10 bp sequence homologous to the consensus binding site of activator protei n-2 (AP-2). Protein complexes derived from U937 and Jurkat cells were found to bind to this element. Competitive EMSA using a consensus AP-2 oligonucleotide indicated that AP-2 may be involved. Functional assay s demonstrate that this region can repress activity of a heterologous promoter in the Jurkat T-cell line, but act as an inducible enhancer o f transcription in U937 cells.