Interferon Regulatory Factor Element and Interferon Regulatory Factor 1 in the Induction of Major Histocompatibility Complex Class I Genes in Neural Cells

Abstract

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 astroyctes, 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 γ-activated factor (GAF) or NF-κB, depending on the inducer, indicating that both γ activation sites (GAS) and κB sites in the IRF-1 promoter are important. These data indicate that the MHC-IRF-E may be the sole functional enhancer of the MHC class I gene and that the regulation of transcription factor IRF-1 activity is involved in the regulation of MHC class I genes in neural cells in response to various stimuli.