Usage of primary cells to delineate IFN-gamma-responsive DNA elements in the HLA-DRA promoter and to identify a novel IFN-gamma-enhanced nuclear factor.
The IFN-gamma regulation of the HLA-DRA gene was examined in a primary cell type, the astrocyte. Site-specific mutagenesis of the DRA promoter reveals that three known sequences, S, X, and Y, are required for an optimal IFN-gamma response. Specifically for the X sequence, the X1, but not the X2, site is involved in IFN-gamma regulation of HLA-DRA in the astrocyte. Most interesting, a novel IFN-gamma-enhanced protein (IFNEX) with specificity for the X element has consistently been observed in nuclear extracts made from primary astrocytes. The correlation of the functional importance of X1 in IFN-gamma-regulated DRA expression and the enhancement of IFNEX by IFN-gamma strongly suggests that IFNEX may play a crucial role in IFN-gamma-regulated class II MHC gene expression.
Moses
H
H
Curriculum in Neurobiology, University of North Carolina, Chapel Hill 27599-7295.
Panek
R B
RB
Benveniste
E N
EN
Ting
J P
JP
D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005802:Genes, MHC Class II; D005910:Glioma; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D051381:Rats; D011919:Rats, Inbred Strains; D012045:Regulatory Sequences, Nucleic Acid
D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D009687:Nuclear Proteins; D007371:Interferon-gamma