The high mobility group protein HMG I(Y) is required for NF-kappa B-dependent virus induction of the human IFN-beta gene.
In this paper, we show that both NF-kappa B and the high mobility group protein I(Y) (HMG I(Y)) are required for virus induction of the human interferon-beta (IFN-beta) gene. NF-kappa B binds to the terminal regions of a 10 bp regulatory sequence through contacts in the major groove. while HMG I(Y) recognizes the central region of the same sequence through contacts in the minor groove. Mutations that interfere with binding of either protein decrease the level of virus induction, and activation of the gene can be blocked by either NF-kappa B or HMG I(Y) antisense RNA. HMG I(Y) stimulates the binding of NF-kappa B to the IFN-beta promoter, and it may also function as a promoter-specific accessory factor for NF-kappa B transcriptional activity.
Thanos
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Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Maniatis
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D000595:Amino Acid Sequence; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D006609:High Mobility Group Proteins / Q000502:physiology*; D006801:Humans; D016899:Interferon-beta / Q000235:genetics*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010222:Parainfluenza Virus 1, Human; D011401:Promoter Regions, Genetic; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D014412:Tumor Virus Infections / Q000235:genetics*
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D016372:RNA, Antisense; D012333:RNA, Messenger; D016899:Interferon-beta