Reversal of intrinsic DNA bends in the IFN beta gene enhancer by transcription factors and the architectural protein HMG I(Y).
In this paper, we investigate DNA bending induced by proteins required for virus induction of the human interferon-beta (IFN beta) gene. We show that NF-kappa B-DNA complexes that are functionally distinct in the context of the IFN beta enhancer are also conformationally distinct and that two sites in the enhancer contain in-phase bends that are counteracted or reversed by the binding of NF-kappa B, ATF-2/c-Jun, and HMG I(Y). Strikingly, this modulation of intrinsic enhancer architecture results in an orientation that favors predicted protein-protein interactions in a functional nucleoprotein complex, the enhanceosome. Furthermore, the subtle modulation of DNA structure by HMG I(Y) in this process distinguishes it from other architectural factors.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
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Falvo
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Thanos
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Maniatis
D051698:Activating Transcription Factor 2; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D015342:DNA Probes; D004270:DNA, Circular / Q000032:analysis / Q000648:ultrastructure; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D015967:Gene Expression Regulation, Viral / Q000235:genetics; D006367:HeLa Cells / Q000502:physiology; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics*; D016350:Leucine Zippers / Q000235:genetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics; D009690:Nucleic Acid Conformation; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014998:Y Chromosome / Q000235:genetics*
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D015342:DNA Probes; D004270:DNA, Circular; D006609:High Mobility Group Proteins; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D016899:Interferon-beta