Nuclear receptors represent a large family of transcriptional factors involved in development, differentiation, homeostasis, and cancer. Nurr1, a member of the orphan nuclear receptor superfamily, was recently demonstrated to be of critical importance in the developing central nervous system, where it is required for the generation of midbrain dopaminergic cell. Although its role during dopaminergic neurogenesis has been extensively studied, its transcriptional regulation of TH, the rate-limiting enzyme of dopamine biosynthesis, is not well understood.
Here we show that Nurr1 directly mediated transcriptional activation or repression of TH gene through NBRE-A site and a key regulating complex of TH expression, that may be formed in NBRE-A site during dopaminergic neurogenesis. In recent years, a growing number of cofactor has been discovered that participate in the regulation of the transcriptional activity of promoter. So, we present the identification of a cofactors binding in and around NBRE-A, which differentially regulates the transcriptional activity of the human TH promoter in human neural stem cell, F3, and human neuroblastoma cell, SH-SY5Y, we are preformed 2-D gel electrophoresis and LC peptide sequencing analysis. Together, these data suggests that Nurr1 and cofactors may regulate differentially transcription activity of TH promoter in neural stem cell and dopaminergic neurons.
Keywords: tyrosine hydroxylase, Nurr1, doapminergic neuron, neural stem cell, neuroblastoma cell.