Epigenetic control of the expression of opioid receptor genes.

Three opioid receptors (ORs) are encoded by three different genes, the mu (MOR), delta (DOR) and kappa (KOR) genes in the OR gene family. The three genes are highly conserved in their structures and regulatory sequences, but expressed in temporally and spatially distinct patterns. Studies using cell models have revealed transcriptional regulation of the three genes by combinatorial, multiple transcription factors and chromatin remodeling and modification factors. Recent results implicated additional epigenetic contribution to the expression of the three OR genes, reflected on the alteration in their DNA methylation patterns and chromatin modifications, along the course of neuronal differentiation. In the retinoic acid-induced neuronal differentiation model, expression of receptors for neurotrophins in differentiating cells appeared to contribute to changes in the epigenetic marks of the promoters of OR genes during the course of neuronal differentiation, and hence the level of OR expression.