Receptor that responds to common pollutants also controls development.

Sartor, MA, M Schnekenburger, JL Marlowe, JF Reichard, Y Wang, Y Fan, C Ma, S Karyala, D Halbleib, X Liu, M Medvedovic and A Puga. 2009. Genome-wide analysis of aryl hydrocarbon receptor binding targets reveals an extensive array of gene clusters that control morphogenetic and developmental programs. Environmental health Perspectives doi:10.1289/ehp.0800485.

A genetic trigger in the cell, long studied for its role in responding to some of the most toxic compounds known, appears to have newly discovered important functions in directing development.

A study published in the journal Environmental Health Perspectives sheds light on the possible dual role of the Ah receptor. The findings show that the receptor can trigger different genes in the presence of pollutants than it does when no pollutants are around.

In this study, researchers used a variety of approaches to demonstrate for the first time that the Ah receptor can control the expression of many gene clusters important in cell development. The Ah receptor has been studied extensively for its role in metabolizing harmful compounds, including polycyclic and halogenated compounds such as dioxins, polychlorinated biphenyls (PCBs) and the carcinogen benzo-a-pyrene. 

These chemicals can activate the Ah receptor, which then signals for the expression of genes involved in taking apart the compounds. Sometimes detoxification is imperfect and results in more toxic substances than the original parent compound – a process known as bioactivation. These imperfections led scientists to believe that some of these detoxification systems have other, unknown roles in the cell.

Using mouse liver cancer cells, the research team examined Ah receptor behavior both with and without pollutants. Without pollutants, the Ah receptor was involved in the expression of genes associated with development. When pollutants were added, the Ah receptor shifted and bound to different portions of DNA - those involved in the expression of metabolism/detoxification genes.

This raises the possibility that exposure in the developing embryo to some of the most toxic compounds known could potentially change gene expression throughout life by altering early developmental processes. Changes in gene expression may foster age-related disease.

From this, the researchers conclude that "the AHR is a likely key regulator of genes with a function during embryonic development" and that "gene-environment interactions during fetal life may be potential triggers of developmental abnormalities."