Identification and characterization of the Hesr1/Hey1 as a candidate trans-acting factor on gene expression through the 3′ non-coding polymorphic region of the human dopamine transporter (DAT1) gene
Identification and characterization of the Hesr1/Hey1 as a candidate trans-acting factor on gene expression through the 3′ non-coding polymorphic region of the human dopamine transporter (DAT1) gene
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DOI：
10.1093/jb/mvi020
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发表时间：
2005-02-01
影响因子：
2.7
通讯作者：
Ishiura, S
中科院分区：
文献类型：
--
作者：
Fuke, S;Sasagawa, N;Ishiura, S
多巴胺转运蛋白（DAT）基因的表达影响多巴胺能神经传递。DAT 1基因3 '端非编码区的可变数目串联重复序列（VNTR）多态性作为顺式元件影响基因表达，并与某些神经精神疾病相关。本研究在酵母单杂交系统中鉴定了碱性螺旋-环-螺旋（basic helix-loop-helix，bHLH）转录因子Hesr 1（Hairy/enhancer of split related transformational factor 1 with a YRPW motif，又称Hey 1/HERP 2/HRT 1/CHF 2）作为一个反式作用因子，并发现Hesr 1在哺乳动物细胞系中与DAT 1基因的3 '端非编码区一起下调报告基因的表达。负调控依赖于bHLH和分子的橙子结构域，而不是YRPW基序。负调控影响VNTR依赖的基因表达差异。此外，我们还鉴定了一个剪接变体Hesr 1 - 12 nt，其活性较低。我们还发现，Hesr 1，C386 A的SNP，导致缺乏活性。这些结果提示Hesr 1基因及其多态性可能与多巴胺相关的多基因疾病和行为特征有关。
Expression of the dopamine transporter (DAT) gene affects dopaminergic neurotransmission. A variable number tandem repeat (VNTR) polymorphism in the 3 ' noncoding 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 ' noncoding 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.