DOWN-REGULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX Q1(B) GENE-EXPRESSION BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN

We analyzed mouse hepatoma cells using differential display to discove r new genes that respond to the environmental contaminant 2,3,7,8-tetr achlorodibenzo-p-dioxin (TCDD). We identified a class I major histocom patibility complex (MHC) gene, which we designated as MHC Q1(b), whose expression decreases in the presence of TCDD. TCDD-induced down-regul ation of MHC Q1(b) requires both the aromatic hydrocarbon receptor and the aromatic hydrocarbon receptor nuclear translocator, transcription factors that up-regulate other genes in response to TCDD. Down-regula tion of MHC Q1(b) by TCDD appears to involve both transcriptional and posttranscriptional regulatory events; the post-transcriptional destab ilization of MHC Q1(b) mRNA is probably a secondary response to TCDD. Our findings reveal new mechanistic aspects of gene regulation by TCDD , In addition, our observations suggest a mechanism that might account for some of TCDD's immunotoxic effects.