THE HIGH-MOBILITY GROUP PROTEIN HMG I(Y) CAN STIMULATE OR INHIBIT DNA-BINDING OF DISTINCT TRANSCRIPTION FACTOR ATF-2 ISOFORMS

The high mobility group protein HMG I(Y) stimulates the binding of a s pecific isoform of the activating transcription factor 2 (ATF-2(195)) to the interferon beta (IFN-beta) gene promoter. HMG I(Y) specifically interacts with the basic-leucine zipper region of ATF-2(195), and HMG I(Y) binds to two sites immediately flanking the ATF-2 binding site o f the IFN-beta promoter. Here, we show that HMG I(Y) can stimulate the binding of ATF-2(195), at least in part, by promoting ATF-2 dimerizat ion. In addition, we report the characterization of a naturally occurr ing isoform of ATF-2 (ATF-2(192)) that binds specifically to the IFN-b eta promoter but is unable to interact with HMG I(Y). Remarkably, HMG I(Y) inhibits the binding of ATF-2(192) to the IFN-beta promoter. Thus , the ability of HMG I(Y) to specifically interact with ATF-2 correlat es with its ability to stimulate ATF-2 binding to the IFN-beta promote r. Comparisons of the amino acid sequences of the basic-leucine zipper domains of ATF-2(195) and ATF-2(192) suggest that HMG I(Y) interacts with a short stretch of basic amino acids near the amino terminus of t he basic-leucine zipper domain of ATF-2(195).