Down-regulation of major histocompatibility complex Q1b gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
We analyzed mouse hepatoma cells using differential display to discover new genes that respond to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We identified a class I major histocompatibility complex (MHC) gene, which we designated as MHC Q1b, whose expression decreases in the presence of TCDD. TCDD-induced down-regulation of MHC Q1b 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-regulation of MHC Q1b by TCDD appears to involve both transcriptional and post-transcriptional regulatory events; the post-transcriptional destabilization of MHC Q1b 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.
Dong
L
L
Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305-5332, USA.
Ma
Q
Q
Whitlock
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001483:Base Sequence; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004268:DNA-Binding Proteins; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D015723:Gene Library; D005805:Genes, MHC Class I / Q000187:drug effects*; D018257:Helix-Loop-Helix Motifs / Q000502:physiology; D006649:Histocompatibility Antigens / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology; D016415:Sequence Alignment; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic
C497397:Arnt protein, mouse; D004268:DNA-Binding Proteins; D006649:Histocompatibility Antigens; C109310:MHC Q1b protein, mouse; D019384:Nucleic Acid Synthesis Inhibitors; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D003609:Dactinomycin; D019363:Cytochrome P-450 CYP1A1