Retinoid X receptor α acts as a negative regulator in Nurr1-induced dopaminergic differentiation in rat neural precursor cells.

To investigate the role of retinoid X receptor (RXRα)–Nurr1 heterodimers in tyrosine hydroxylase (TH) expression, we observed retrovirus-induced RXRα–Nurr1 heterodimer interactions with, and transactivation of, the TH promoter region in cultured rat embryonic neural precursor cells. Interestingly, forced expression of RXRα with Nurr1 remarkably reduced Nurr1 activity in TH+ dopaminergic neuron generation and significantly down-regulated TH promoter activity. These regulatory activities were altered in both Nurr1dim- and RXRαdim- that disrupted dimeric binding, verifying that the Nurr1–RXRα heterodimer represses TH promoter activity. Therefore, a plausible explanation for the inhibitory role of RXRα in Nurr1-induced TH expression is that RXRα differentially affects an inhibitory element of the TH promoter.