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 specific 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 of 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 dimerization. In addition, we report the characterization of a naturally occurring isoform of ATF-2 (ATF-2(192)) that binds specifically to the IFN-beta 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 correlates with its ability to stimulate ATF-2 binding to the IFN-beta promoter. 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 the basic-leucine zipper domain of ATF-2(195).
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138.
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D051698:Activating Transcription Factor 2; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D025741:HMGA1a Protein; D006609:High Mobility Group Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000235:genetics; D016350:Leucine Zippers; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011994:Recombinant Proteins; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors; D016335:Zinc Fingers
D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D046911:Macromolecular Substances; D016328:NF-kappa B; D011994:Recombinant Proteins; D014157:Transcription Factors; D025741:HMGA1a Protein; D016899:Interferon-beta; D004247:DNA