Epigenetics and PCBs

Epigenetic links genetics and environment in shaping several physiological mechanisms including endocrine functions. Growing evidences suggest an interplay among endocrine system, environment, and epigenetics in the etiology of many complex diseases, including some neuropsychiatric disorders. We have demonstrated that a prenatal exposure to polychlorinated biphenyls (PCBs) is able to modulate some epigenetic marks related to the steroid receptors, which (in particular androgen receptor, AR) are cofactors of histone remodeling enzymes; in our recent paper we focused on the interaction between PCBs–AR and the demethylase Jarid1b. Our studies indicate that PCBs induce AR transactivation in a dose-dependent way. Jarid1b potentiates transcriptional activity independently of ligand and of cell phenotype; in particular, Jarid1b increase the AR transactivation in the isoforms with a short polyQ expansion, which are normally present in the population. Since an inverse relationship appears to exist between the AR transcriptional activity and the polyQ repeat length, it is possible to hypothesize that Jarid1b–AR interaction strength depends on the polyQ lenght. PCBs auto-downregulate AR expression and this negative feedback is potentiated by Jarid1b and depends on AR promoter length. These results open new perspectives in the PCBs/AR/Jarid1b interplay possibly occurring in the pathogenesis of some neurological diseases like autism.