INTERACTION OF THE CNC-BZIP FACTOR TCF11 LCR-F1/NRF1 WITH MAFG - BINDING-SITE SELECTION AND REGULATION OF TRANSCRIPTION/

We have previously shown that the widely expressed human transcription factor TCF11/LCR-F1/Nrf1 interacts with small Maf proteins and binds to a subclass of AP1-sites, Such sites are required for beta-globin 5' DNase hypersensitive site 2 enhancer activity, erythroid porphobilino gen deaminase inducibility, hemin responsiveness by heme-oxygenase 1 a nd expression of the gene NAD(P)H:quinone oxidoreductase(1), Here we r eport the optimal DNA-binding sequences for TCF11/LCR-F1/Nrf1 alone an d asa heterodimer with MafG, identified by using binding-site selectio n, The heterodimer recognises a 5'-TGCTgaGTCAT-3' binding-site that is identical to the established Nf-E2-site, the antioxidant response ele ment and the heme-responsive element while the binding specificity of the homomer is less stringent. To investigate the activity of TCF11 th rough this selected site,both alone and in the presence of MafG, we ha ve used a transient transfection assay, TCF11 alone activates transcri ption white MafG alone acts as a repressor. When coexpressed, MafG int erferes with TCF11 transactivation in a dose dependent manner, This in dicates that MafG protein, which heterodimerises efficiently with TCF1 1 in vitro (the heterodimer having a higher affinity for DNA than TCF1 1 alone), does not co-operate with TCF11 in transactivating transcript ion. We propose that since both these factors are widely expressed, th ey may act together to contribute to the negative regulation of this s pecific target site. Efficient positive regulation by TCF11 may requir e alternative partners with perhaps more restricted expression pattern s.