FOS AND JUN REPRESS TRANSCRIPTION ACTIVATION BY NF-IL6 THROUGH ASSOCIATION AT THE BASIC ZIPPER REGION

NF-IL6 and AP-1 family transcription factors are coordinately induced by interleukin-6 (IL-6) in a cell-type-specific manner, suggesting tha t they mediate IL-6 signals in the nucleus. We show that the basic leu cine zipper (bZIP) region of NF-IL6 mediates a direct association with the bZIP regions of Fos and Jun in vitro. This interaction does not d epend on the presence of their cognate recognition DNA elements or the posttranslational modification of either partner. NF-IL6 homodimers c an bind to both NF-IL6 and AP-1 sites, whereas Fos and Jun cannot bind to most NF-IL6 sites. Cross-family association with Fos or with Jun a lters the DNA binding specificity of NF-IL6 and reduced its binding to NF-IL6 sites. NF-IL6 isoforms that differ in the site of translation initiation have distinct transcriptional activities. Activation of a r eporter gene linked to the NF-IL6 site by NF-IL6 is repressed by Fos a nd by Jun in transient transfection assays. Thus, association with AP- 1 results in repression of transcription activation by NF-IL6. The rep ression is NF-IL6 site dependent and may have a role in determining th e promoter and cell type specificity in IL-6 signaling.