Mechanisms of transcriptional synergism between distinct virus-inducible enhancer elements.
The high mobility group protein HMG I(Y) and the transcription factor NF-kappa B are required for the activity of positive regulatory domain II (PRDII), a virus-inducible regulatory element of the human interferon-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 activating transcription factor 2 (ATF-2) and the assembly of inducible complexes containing ATF-2 and c-Jun. Remarkably, HMG I(Y) also specifically interacts with the leucine zipper/basic region of ATF-2, and ATF-2 in turn interacts with NF-kappa B. We therefore propose that the HMG I(Y) plays a critical structural role in establishing transcriptional synergy between PRDII and PRDIV by promoting the activities and/or binding of NF-kappa B and ATF-2 and by facilitating their interaction.
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
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D051698:Activating Transcription Factor 2; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D015967:Gene Expression Regulation, Viral; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics*; D007739:L Cells; D051379:Mice; D008961:Models, Structural; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D006609:High Mobility Group Proteins; D016328:NF-kappa B; D014157:Transcription Factors; D016899:Interferon-beta