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Human dopamine transporter gene: variation and transcriptional regulation

Human dopamine transporter gene: variation and transcriptional regulation
人类多巴胺转运蛋白基因:变异和转录调控
批准号:
9815162
负责人:
Zhicheng Carl Lin
金额:
$41.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2007
资助国家:
美国
项目状态:
已结题
起止时间:
2007-09-01 至 2024-07-31

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中文摘要
翻译
这项更新提案的总体目标是剖析人类基因转录机制, 多巴胺转运蛋白基因(hDAT)。多巴胺转运蛋白(DAT)调节多巴胺转运蛋白的时空域。 通过多巴胺的再摄取和释放的多巴胺神经传递并因此有助于运动, 动机、认知和注意力、工作记忆、行为组织和激素释放。公 认识到DAT基因在大脑中的表达是高度限制的,在个体之间是不同的, 受试者,并可以调节内源性和外源性因素,如物质的使用和压力。 DAT表达改变可能导致hDAT相关的病理生理状态,如物质使用 疾病(SUD)。然而,关于hDAT表达如何调节以及DNA序列如何调节的信息, 变异影响的调节表达在很大程度上仍然是零星的。在这个实验中要检验的假设 提出新的转录因子(TF)在通过紊乱- 相关的顺式作用位点。我们的初步研究表明,TF可以调节hDAT启动子, 互动的方式。因此,本项目的三个具体目标是:1)证明RNA-蛋白质复合物 2)证实TF介导的5'和3'顺式作用位点之间的拮抗作用; 和3)鉴定结合两个功能性VNTR用于启动子调节的TF。结果将增加基本的 了解hDAT受信号通路调节的前导位点,并赋予相关风险 大脑紊乱
英文摘要
The overall goal of this renewal proposal is to dissect genetic transcription mechanisms in the human dopamine transporter gene (hDAT). The dopamine transporter (DAT) regulates the spatio-temporal domains of dopamine neurotransmission by reuptake and release of dopamine and thus contributes to locomotion, motivation, cognition and attention, working memory, behavioral organization and hormone release. It is well recognized that expression of the DAT gene in the brain is highly circumscribed, varies among individual subjects and can be regulated by endogenous and exogenous factors such as substance uses and stress. Altered DAT expression may contribute to hDAT-associated pathophysiological states such as substance use disorders (SUDs). However, information about how hDAT expression is regulated and how DNA sequence variation influences the regulated expression remains largely sporadic. The hypothesis to be tested in this proposal is that novel transcription factors (TFs) play a major role in regulating the hDAT promoter via disorder- associated cis-acting sites. Our preliminary studies show that TFs may regulate the hDAT promoter in an interactive manner. Therefore, three specific aims of this project are to: 1) demonstrate a RNA-protein complex involved in the promoter regulation; 2) confirm a TF-mediated antagonism between 5’ and 3’ cis-acting sites; and 3) identify TFs that bind to two functional VNTRs for promoter regulation. The results will add fundamental knowledge on lead sites through which hDAT is regulated by signaling pathways and confers risks for related brain disorders.
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Monitoring DAT in Live Rats
  • 批准号:
    8440730
  • 项目类别:
  • 资助金额:
    $18.96万
  • 财政年份:
    2012
  • 负责人:
    Zhicheng Carl Lin
  • 依托单位:
Monitoring DAT in Live Rat
  • 批准号:
    8322983
  • 项目类别:
  • 资助金额:
    $19.75万
  • 财政年份:
    2012
  • 负责人:
    Zhicheng Carl Lin
  • 依托单位:
Human dopamine transporter gene: variation and transcriptional regulation
  • 批准号:
    10472586
  • 项目类别:
  • 资助金额:
    $41.0万
  • 财政年份:
    2007
  • 负责人:
    Zhicheng Carl Lin
  • 依托单位:
Human Dopamine Transporter Gene: Variation and Transcriptional Regulation
  • 批准号:
    8675815
  • 项目类别:
  • 资助金额:
    $24.89万
  • 财政年份:
    2007
  • 负责人:
    Zhicheng Carl Lin
  • 依托单位:
海外基金