MECHANISMS OF TRANSCRIPTIONAL SYNERGISM BETWEEN DISTINCT VIRUS-INDUCIBLE ENHANCER ELEMENTS

The high mobility group protein HMG I(Y) and the transcription factor NF-kappaB are required for the activity of positive regulatory domain II (PRDII), a virus-inducible regulatory element of the human interfer on-beta gene promoter. In this paper we provide evidence that HMG I(Y) is also required for the activity of PRDIV, a regulatory element that synergizes with PRDII. In this case, HMG I(Y) stimulates binding of a ctivating transcription factor 2 (ATF-2) and the assembly of inducible complexes containing ATF-2 and c-Jun. Remarkably, HMG I(Y) also speci fically interacts with the leucine zipper/basic region of ATF-2, and A TF-2 in turn interacts with NF-kappaB. We therefore propose that the H MG I(Y) plays a critical structural role in establishing transcription al synergy between PRDII and PRDIV by promoting the activities and/or binding of NF-kappaB and ATF-2 and by facilitating their interaction.