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|Title:||Characterization of NPAS1, a transcription factor that regulates tyrosine hydroxylase expression during dopaminergic neuron development||Authors:||TEH HUI LENG, CHRISTINA||Keywords:||NPAS1, nuclear localization, tyrosine hydroxylase, transcription repression, dopaminergic neuron, development||Issue Date:||5-Jun-2006||Citation:||TEH HUI LENG, CHRISTINA (2006-06-05). Characterization of NPAS1, a transcription factor that regulates tyrosine hydroxylase expression during dopaminergic neuron development. ScholarBank@NUS Repository.||Abstract:||Dysfunctioning of dopaminergic (DA) neurons is related to schizophrenia and Parkinsona??s disease. Therefore, much research has been carried out in understanding the development of these DA neurons. In this study, we employ an immature dopaminergic cell line, MN9D to identify genes that are up-regulated when the cells are induced to differentiate with 1 mM n-butyric acid. One of the genes identified is neuronal PAS domain protein 1 (NPAS1). Expression studies showed that NPAS1 is found in the mouse ventral midbrain from E11.5 onwards. Domains analysis revealed that a NES within NPAS1 excludes it from the nucleus and nuclear localization of NPAS1 requires ARNT. Further analysis identified two non-overlapping repression domains within NPAS1. Furthermore, over-expression and siRNA experiments revealed that NPAS1 is able to down-regulate the expression of tyrosine hydroxylase, the rate-limiting enzyme required for synthesis of catecholamines. This down-regulation is due to a direct binding of NPAS1 to the TH promoter. These findings provide new insight into role of NPAS1 during the developmental process of ventral midbrain DA neurons, the significance of which is discussed.||URI:||http://scholarbank.nus.edu.sg/handle/10635/15411|
|Appears in Collections:||Ph.D Theses (Open)|
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