Dioxin-responsive AHRE-II gene battery: identification by phylogenetic footprinting.
We identified a set of genes that respond to dioxins through the recently discovered AHRE-II ("XRE-II") enhancer element. A total of 36 genes containing AHRE-II motifs conserved across human, mouse, and rat gene orthologs were identified by genome-wide transcription-factor binding-site searches and phylogenetic footprinting. Microarray experiments on liver from rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin revealed statistically significant changes in mRNA levels for 13 of these 36 genes after three hours and 15 genes after 19h. The set of responsive genes was functionally characterized by ontological analysis and found to be enriched in ion-channels and transporters. Our identification of 36 putatively AHRE-II-regulated genes highlights the regulatory versatility of the aryl hydrocarbon receptor (AHR) and the ability of the AHR and its dimerization partner, ARNT, to act both as a ligand-activated transcription-factor (on AHRE-I) and as a ligand-activated coactivator (on AHRE-II). Collectively, these results demonstrate that the AHRE-II induction mechanism is employed by multiple genes and provide the first categorization of the gene battery of a ligand-activated coactivator.
Boutros
Paul C
PC
Department of Pharmacology, University of Toronto, Toronto, Ont., Canada M5S 1A8.
Moffat
Ivy D
ID
Franc
Monique A
MA
Tijet
Nathalie
N
Tuomisto
Jouko
J
Pohjanvirta
Raimo
R
Okey
Allan B
AB
D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001665:Binding Sites; D018983:DNA Footprinting / Q000379:methods; D004268:DNA-Binding Proteins / Q000378:metabolism; D004147:Dioxins; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D016678:Genome; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
C497396:ARNT protein, human; C497398:ARNT protein, rat; C497397:Arnt protein, mouse; D004268:DNA-Binding Proteins; D004147:Dioxins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator