# Human dopamine transporter gene: variation and transcriptional regulation

> **NIH NIH R01** · MCLEAN HOSPITAL · 2020 · $410,000

## Abstract

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.

## Key facts

- **NIH application ID:** 9983686
- **Project number:** 5R01DA021409-12
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** Zhicheng Carl Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $410,000
- **Award type:** 5
- **Project period:** 2007-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983686

## Citation

> US National Institutes of Health, RePORTER application 9983686, Human dopamine transporter gene: variation and transcriptional regulation (5R01DA021409-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9983686. Licensed CC0.

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