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

Abstract

To investigate the role of retinoid X receptor alpha (RXR alpha)-Nurr1 heterodimers in tyrosine hydroxylase (TH) expression, we observed retrovirus-induced RXR alpha-Nurr1 heterodimer interactions with, and transactivation of, the TH promoter region in cultured rat embryonic neural precursor cells. Interestingly, forced expression of RXR alpha 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 Nurr1(dim-) and RXR alpha(dim-) that disrupted dimeric binding, verifying that the Nurr1-RXR alpha heterodimer represses TH promoter activity. Therefore, a plausible explanation for the inhibitory role of RXR alpha in Nurr1-induced TH expression is that RXR alpha differentially affects an inhibitory element of the TH promoter. NeuroReport 21: 1162-1166 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.