Aryl hydrocarbon receptor-induced activation of the human IGH hs1.2 enhancer: Mutational analysis of putative regulatory binding motifs.

The human hs1.2 enhancer within the Ig heavy chain gene (IGH) is polymorphic and associated with a number of autoimmune diseases. The polymorphic region is characterized by tandem repeats of an ∼53-bp invariant sequence containing possible binding sites for several transcription factors.

A dioxin response element in the multiple cloning site of the pGL3 luciferase reporter influences transcriptional activity.

Luciferase reporter plasmids (pGL3 backbone, Promega) have been utilized to characterize the transcriptional effects of the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon receptor (AhR) ligands. Following ligand activation, the AhR and its dimerization partner AhR nuclear translocator (ARNT) regulate transcription by binding dioxin response elements (DREs) in regulatory regions of dioxin-sensitive genes. Upon sequencing of our luciferase reporters, we unexpectedly identified a DRE core motif within the multiple cloning site (mcsDRE) of the pGL3 luciferase plasmid backbone in a subset of our reporters.

2,3,7,8-tetrachlorodibenzo-p-dioxin induces transcriptional activity of the human polymorphic hs1,2 enhancer of the 3'Igh regulatory region.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxicant known to inhibit Ab secretion and Ig expression. Inhibition of Ig expression may be partially mediated through repression of the 3'Igh regulatory region (3'IghRR). TCDD inhibits mouse 3'IghRR activation and induces aryl hydrocarbon receptor binding to dioxin response elements within the 3'IghRR enhancers hs1,2 and hs4.