A promoter can be regulated by various cis-acting elements so that delineation of the regulatory modes among them may help understand developmental, environmental and genetic mechanisms in gene activity. Here we report that the human dopamine transporter gene SLC6A3 carries a 5' distal 5-kb super enhancer (5KSE) which upregulated the promoter by 5-fold. Interestingly, 5KSE is able to prevent 3' downstream variable number tandem repeats (3'VNTRs) from silencing the promoter. This new enhancer consists of a 5'VNTR and three repetitive sub-elements that are conserved in primates. Two of 5KSE's sub-elements, E-9.7 and E-8.7, upregulate the promoter, but only the later could continue doing so in the presence of 3'VNTRs. Finally, E-8.7 is activated by novel dopaminergic transcription factors including SRP54 and Nfe2l1. Together, these results reveal a multimodal regulatory mechanism in SLC6A3.

• MeSH
• biologické modely MeSH
• dospělí MeSH
• genetická transkripce * MeSH
• haplotypy genetika   MeSH
• lidé MeSH
• minisatelitní repetice genetika   MeSH
• myši inbrední C57BL MeSH
• nádorové buněčné linie MeSH
• promotorové oblasti (genetika) * MeSH
• proteiny přenášející dopamin přes plazmatickou membránu genetika   MeSH
• transkripční faktory metabolismus   MeSH
• zesilovače transkripce MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH