title: Identification of an intronic cis-acting element in the human dopamine transporter gene.
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.
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA 02478, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Nian
authors.initials: N
authors.lastname: Xiong
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Lin
mesh_terms: D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D002460:Cell Line; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D007438:Introns / Q000235:genetics*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013539:Simian virus 40 / Q000235:genetics
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D009687:Nuclear Proteins; C493214:SLC6A3 protein, human