Exp Neurobiol 2005; 14(1): 41-47

Published online July 1, 2005

© The Korean Society for Brain and Neural Sciences

Activation of the Tyrosine Hydroxylase Promoter by NeuroD in Neural Stem Cells

Il-Sun Kwon1, Jung-Mi Choi1, Kyong-Tai Kim3, Seung U Kim2, Young-Don Lee1 and Haeyoung Suh-Kim1*

1Department of Anatomy, 2Brain Disease Research Center, Ajou University School of Medicine, Suwon 443-721, 3Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang 790-784, Korea

Correspondence to: *To whom correspondence should be addressed.
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Transcription of the rat tyrosine hydroxylase (TH) gene is controlled by enhancer sequences in its 5' flanking region; these enhancers include the AP1-, AP2-, dyad-, POU/Oct- binding domain, and cAMP response element (CRE) motifs. Of cis-regulatory elements, a putative E-box is located at -190 bp on the 5' flanking region of TH. In this study, we investigated whether the TH gene expression is regulated by bHLH transcription factors such as NeuroD or neurogenin 1. We used mouse neural stem cells, A3B1L6, immortalized with v-myc. In A3B1L6 cells, protein kinase A (PKA) increased TH activity. The stimulatory effect of PKA was dependent on a CRE located at -45 bp from the site of transcription initiation, suggesting that A3B1L6 provides an appropriate system for the study of TH gene expression. Importantly, coexpression of NeuroD or neurogenin 1 with a ubiquitous bHLH partner E47 could transactivate the TH promoter. The data indicate that expression of the TH gene may be regulated by bHLH transcription factors probably through the E-box at -190.

Keywords: tyrosine hydroxylase (TH), neural stem cell, NeuroD, PKA, CREB