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Biochem Biophys Res Commun. 2009 Jul 24;385(2):263-8. doi: 10.1016/j.bbrc.2009.05.060. Epub 2009 May 19.

Activation function 2 mediates dioxin-induced recruitment of estrogen receptor alpha to CYP1A1 and CYP1B1.

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Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ont, Canada.


We investigated the role of the activation function 1 (AF1) and AF2 domains of estrogen receptor alpha (ERalpha) in mediating dioxin-dependent recruitment of ERalpha to cytochrome P4501A1 (CYP1A1) and CYP1B1 in HuH-7 human hepatoma cells. Dioxin-induced recruitment of ERalpha wildtype (ERalpha-WT) and an ERalpha AF1 deletion mutant (ERalpha-DeltaAF1), but not a transcriptional inactive AF2 mutant (ERalpha-AF2mut) to CYP1A1 and CYP1B1. Direct interactions between AHR and the AF1 and AF2 domains of ERalpha were observed, and were independent of mutations in the AF2. Expression of ERalpha-WT increased dioxin-induced CYP1A1 and CYP1B1-regulated reporter activity, and CYP1A1 and CYP1B1 mRNA levels. However, no increases in gene expression above vector controls were observed in cells transfected with ERalpha-DeltaAF1 or ERalpha-AF2mut. Our data show that the AF2 domain contributes to dioxin-induced recruitment of ERalpha to AHR target genes, but that both the AF1 and AF2 domains are required for ERalpha-dependent increases in AHR activity.

[Indexed for MEDLINE]

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