Back to Search
Start Over
Differential effects of the HESR/HEY transcription factor family on dopamine transporter reporter gene expression via variable number of tandem repeats.
- Source :
-
Journal of neuroscience research [J Neurosci Res] 2011 Apr; Vol. 89 (4), pp. 562-75. Date of Electronic Publication: 2011 Feb 02. - Publication Year :
- 2011
-
Abstract
- The 3'-untranslated region (UTR) of the human dopamine transporter (DAT1) gene contains a variable number of tandem repeats (VNTR) domain, which is thought to be associated with dopamine-related psychiatric disorders, personality, and behavior. However, the molecular and neuronal functions of polymorphisms within the VNTR domain are unknown. We previously identified the transcription factor HESR1 (HEY1) as a VNTR-binding protein. Hesr1 knockout mice exhibit DAT up-regulation in the brain and low levels of spontaneous activity. Other members of the HESR (HEY) family, including HESR2 (HEY2) and 3 (HEYL), have similar DNA-binding domains. In this study, we analyzed the effects of HESR1, -2, and -3 on DAT1 expression in human neuroblastoma SH-SY5Y cells using luciferase reporter assays. We found that the VNTR domain played an inhibitory role in DAT1 reporter gene expression and that HESR1 and -2 inhibited expression via both the core promoter and the VNTR. The inhibitory effects of HESR family members on DAT reporter gene expression differed depending on the number of repeats in the VNTR domain. We also found that each Hesr was expressed in the dopaminergic neurons in the mouse midbrain. These results suggest that the HESR family is involved in DAT expression via the VNTR domain.<br /> (Copyright © 2011 Wiley-Liss, Inc.)
- Subjects :
- Animals
Base Sequence
Cell Line, Tumor
Dopamine Plasma Membrane Transport Proteins biosynthesis
Gene Expression
Gene Expression Profiling
Humans
Immunohistochemistry
Male
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Neurons physiology
Polymorphism, Genetic
Transfection
Basic Helix-Loop-Helix Transcription Factors genetics
Cell Cycle Proteins genetics
Dopamine Plasma Membrane Transport Proteins genetics
Gene Expression Regulation genetics
Repressor Proteins genetics
Tandem Repeat Sequences genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4547
- Volume :
- 89
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of neuroscience research
- Publication Type :
- Academic Journal
- Accession number :
- 21290414
- Full Text :
- https://doi.org/10.1002/jnr.22593