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Identification of an intronic cis-acting element in the human dopamine transporter gene

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Abstract

The human dopamine transporter gene (hDAT) encodes the dopamine transporter in dopamine (DA) neurons to regulate DA transmission. hDAT expression varies significantly from neuron to neuron, and from individual to individual so that dysregulation of hDAT is related to many neuropsychiatric disorders. It is critical to identify hDAT-specific cis-acting elements that regulate the hDAT expression. Previous studies showed that hDAT Intron 1 displayed inhibitory activity for reporter gene expression. Here we report that the hDAT Intron 1 contains a 121-bp fragment that down-regulated both SV40 and hDAT promoter activities by 80% in vitro. Subfragments of 121-bp still down-regulated the SV40 promoter but not the hDAT promoter, as supported by nuclear protein-binding activities. Collectively, 121-bp is a silencer in vitro that might coordinate with transcriptional activities both inside and outside 121-bp in regulation of hDAT.

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Acknowledgments

We are grateful to Dr. A. P. Kouzmenko for providing a genomic clone. This research was supported by U.S. National Institutes of Health grant R01DA021409 (to Z.L.), by a Foundation for University Yong Key Teacher by The Education Department of Henan Province China, 2008 (to YZ), and National Nature Science Fundation of China 81100956 (to YZ).

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Authors and Affiliations

  1. Department of Psychiatry, Harvard Medical School, Boston, MA, USA

    Ying Zhao, Yanhong Zhou, Nian Xiong & Zhicheng Lin

  2. Division of Alcohol and Drug Abuse, McLean Hospital, Mailstop 318, 115 Mill Street, Belmont, MA, 02478, USA

    Ying Zhao, Yanhong Zhou, Nian Xiong & Zhicheng Lin

  3. School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, China

    Ying Zhao

  4. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Nian Xiong

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  1. Ying Zhao
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  2. Yanhong Zhou
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  3. Nian Xiong
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  4. Zhicheng Lin
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Correspondence to Zhicheng Lin.

Additional information

Ying Zhao and Yanhong Zhou contributed equally to this work.

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Zhao, Y., Zhou, Y., Xiong, N. et al. Identification of an intronic cis-acting element in the human dopamine transporter gene. Mol Biol Rep 39, 5393–5399 (2012). https://doi.org/10.1007/s11033-011-1339-4

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  • DOI: https://doi.org/10.1007/s11033-011-1339-4

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