The competitive binding of STAT3 and NF-kappaB on an overlapping DNA binding site.

Interleukin-1 (IL-1) and interleukin-6 (IL-6), two early-response cytokines expressed during an acute inflammatory reaction, regulate the expression of several acute phase proteins (APP) in the liver. IL-1 relays its signal to specific genes via NF-kappaB, whereas IL-6 sends its signal to the nucleus via STAT1alpha and STAT3. Interestingly, overlapping binding sites for STAT3 and NF-kappaB can be found on promoters of several APP genes. We show here that both STAT3 and NF-kappaB are active during inflammation and are capable of binding to a STAT3/NF-kappaB overlapping DNA motif derived from the alpha2-macroglobulin gene promoter. In vitro binding assays demonstrated that NF-kappaB competes with STAT3 binding on this probe. Our results suggest that these transcription factors regulate each others' function through competition for overlapping DNA binding sites.