Induction of the murine class-II antigen-associated invariant chain by TNF-alpha is controlled by an NF-kappa B-like element.
The murine class-II antigen-associated invariant chain (Ii) is a glycoprotein whose synthesis is co-regulated with the major histocompatibility class-II antigens. The Ii mRNA is inducible by tumor necrosis factor-alpha (TNF-alpha). An NF-kappa B protein-binding site (NBS), located in the Ii promoter at bp -121 to -111, confers TNF-alpha inducibility on chimeric reporter constructs expressing the human growth hormone-encoding gene. A distal NF-kappa B-like protein-binding site (NBLS) located at bp -167 to -157 is not required for TNF-alpha inducibility, and deletion of this distal NBLS results in increased constitutive, as well as TNF-alpha-induced, expression of the reporter gene. The NBS is well protected during DNase I footprinting assays and specifically binds proteins in electrophoretic mobility shift assays. A distinct protein-DNA complex is observed when nuclear extracts from TNF-alpha-treated L-cells are used; this complex is not seen in extracts from untreated cells.
Kolk
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DP
Department of Zoology, Arizona State University, Tempe 85287.
Floyd-Smith
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D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D005786:Gene Expression Regulation; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C045084:invariant chain; D004247:DNA