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The Ah-receptor (AHR) is a ligand activated transcription factor that mediates the biological effects of agonists. AHR dimerizes with a structurally related protein known as ARNT (arylhydrocarbon-receptor nuclear transducer). This heterodimer binds enhancer elements and induces the expression of target genes, specifically those involved in the metabolism of xenobiotics. ARNT1 and ARNT2 are members of the basic-helix-loop-helix-PAS family of heterodimeric transcription factors, which also includes AHR, hypoxia-inducible factor-1α (HIF-1α), and the Drosophila single-minded protein (Sim). While ARNT2 expression is limited to brain and kidney, ARNT1 exhibits ubiquitous expression. A targeted disruption of the Arnt locus in the mouse yields embryonic stem cells that fail to activate genes that normally respond to low oxygen tension. Arnt -/- embryos do not survive and show defective angiogenesis of the yolk sac and branchial arches, stunted development, and wasting. Thus, in addition to its regulation of xenobiotic metabolism genes, ARNT is thought to induce developmental gene expression resulting in vascularization of the developing embryo.Immunofluorescence, Western Blotting
