Abstract
Expression of the dopamine transporter (DAT) gene affects dopaminergic neurotransmission. A variable number tandem repeat (VNTR) polymorphism in the 3' non-coding region of the human DAT (DAT1) gene has been reported to affect gene expression as a cis-element, and is associated with some neuropsychiatric disorders. In this study, we identified the basic helix-loop-helix (bHLH) transcriptional factor Hesr1 (the Hairy/enhancer of split related transcriptional factor 1 with a YRPW motif, also named Hey1/HERP2/HRT1/CHF2) as a trans-acting factor in a yeast one-hybrid system, and showed that Hesr1 down-regulates reporter gene expression with the 3' non-coding region of DAT1 gene in mammalian cell lines. The negative regulations depend on bHLH and the Orange domain of the molecule, but not the YRPW motif. The negative regulations affect the VNTR-dependent differences in gene expression. In addition, we identified a splice variant, Hesr1-12nt, with a lower activity. We also show that SNP of Hesr1, C386A, causes a lack of activity. These results suggest that Hesr1 and its polymorphism(s) might be involved in dopamine-related polygenic disorders and behavioral traits.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
