The Ah receptor recognizes DNA binding sites for the B cell transcription factor, BSAP: a possible mechanism for dioxin-mediated alteration of CD19 gene expression in human B lymphocytes.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits murine and human B lymphocyte immunoglobulin production through an unknown mechanism. This study investigated the effect of TCDD on expression of the CD19 gene in a human B lymphocyte cell line. Northern blot analysis showed that TCDD treatment decreased steady state levels of CD19 mRNA by 67% in the IM-9 cell line. Using a gel mobility shift assay, we identified a DNA-binding complex in IM-9 nuclear extracts that by several criteria appears to be the Ah receptor. In addition, the Ah receptor complex recognized a DNA binding site for B cell lineage-specific activator protein (BSAP) in the promoter region of the human CD19 gene which is similar to the consensus Ah receptor DNA binding site. These results suggest that the AhR could interfere with BSAP-stimulated CD19 gene transcription by competition for a common DNA binding site.
Masten
S A
SA
Department of Pharmacology and Therapeutics, University of Florida, Gainesville 32610-0267, USA.
Shiverick
K T
KT
D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000096:biosynthesis*; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016384:Consensus Sequence; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D015345:Oligonucleotide Probes; D051757:PAX5 Transcription Factor; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; C497282:Pax5 protein, mouse; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D004247:DNA; D003577:Cytochrome P-450 Enzyme System