Interferon regulatory factor element and interferon regulatory factor 1 in the induction of major histocompatibility complex class I genes in neural cells.
The role of the MHC-IRF-E and interferon regulatory factor 1 (IRF-1) in the regulation of MHC class I genes in astrocytes was analyzed. Transcriptional activation of MHC class I genes after treatment of astrocytes with various inducers occurred over a period of hours and correlated with cell surface expression. Functional analysis of the MHC class I gene promoter region confirmed that induction was controlled by a restricted region of 88 base pairs containing two well-defined inducible enhancers, the MHC-CRE and the MHC-IRF-E. Further analysis showed that potential MHC-CRE enhancer activity was silent. Therefore, the MHC-IRF-E, rather than the MHC-CRE, appeared responsible for enhancement of the MHC class I gene and was supported by three findings: (1) site-directed mutation of the MHC-IRF-E-abrogated induction, (2) promoter constructs containing IRF-Es as the sole enhancers were highly inducible in astrocytes, and (3) the expression of transcription factor IRF-1, which acts through the MHC-IRF-E to induce MHC class I genes, was induced to high levels in parallel with that of MHC class I induction. The induction of the IRF-1 gene correlated with the prior induction of the gamma-activated factor (GAF) or NF-kappa B, depending on the inducer, indicating that both gamma activation sites (GAS) and kappa B sites in the IRF-1 promoter are important.(ABSTRACT TRUNCATED AT 250 WORDS)
State University of New York, Health Science Center, Department of Neurology, Syracuse 13210, USA.
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D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001483:Base Sequence; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000502:physiology*; D005805:Genes, MHC Class I; D050856:Interferon Regulatory Factor-1; D051379:Mice; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors