Characterization of astrocyte nuclear proteins involved in IFN-gamma- and TNF-alpha-mediated class II MHC gene expression.
IFN-gamma is a potent inducer of class II MHC Ags on different cell types, including the astrocyte. TNF-alpha alone has no effect on class II MHC expression, but enhances IFN-gamma-induced class II expression. IFN-gamma acts by inducing transcription of the class II gene, and TNF-alpha enhances the rate of IFN-gamma-induced transcription. We have previously described two factors, IFN-gamma-enhanced factor X (IFNEX) and TNF-alpha induced complex X (TIC-X), whose expression is induced by IFN-gamma and IFN-gamma/TNF-alpha, respectively, which interacted with the X box of the DRA promoter. In this study, we show that IFNEX and TIC-X bind to the X2 core, with contacts extending into the 3' end of X1 and into the spacer region of the DRA promoter. We also show a functional correlation between binding activity and transcriptional activity of the DRA promoter. These results strongly suggest that both IFNEX and TIC-X play important roles in the regulation of class II MHC gene expression in the astrocyte.
Department of Cell Biology, University of Alabama at Birmingham 35294.
R B
RB
Panek
Y J
YJ
Lee
Y
Y
Itoh-Lindstrom
J P
JP
Ting
E N
EN
Benveniste
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis* / Q000235:genetics; D007371:Interferon-gamma / Q000502:physiology*; D008745:Methylation; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000502:physiology*; D011401:Promoter Regions, Genetic; D051381:Rats; D014157:Transcription Factors / Q000502:physiology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma