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Intragenic Transcriptional cis-Antagonism Across SLC6A3
Y. Zhao, J. Yu, J. Zhao, X. Chen, N. Xiong, T. Wang, H. Qing, Z. Lin,
Language English Country United States
Document type Journal Article
Grant support
DA021409
National Institutes of Health
DA031573
National Institutes of Health
R01 DA021409
NIDA NIH HHS - United States
R21 DA031573
NIDA NIH HHS - United States
NLK
ProQuest Central
from 2019-01-01 to 1 year ago
Medline Complete (EBSCOhost)
from 2010-02-01 to 1 year ago
Health & Medicine (ProQuest)
from 2019-01-01 to 1 year ago
Psychology Database (ProQuest)
from 2019-01-01 to 2019-12-31
- MeSH
- Models, Biological MeSH
- Adult MeSH
- Transcription, Genetic * MeSH
- Haplotypes genetics MeSH
- Humans MeSH
- Minisatellite Repeats genetics MeSH
- Mice, Inbred C57BL MeSH
- Cell Line, Tumor MeSH
- Promoter Regions, Genetic * MeSH
- Dopamine Plasma Membrane Transport Proteins genetics MeSH
- Transcription Factors metabolism MeSH
- Enhancer Elements, Genetic MeSH
- Animals MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
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.
References provided by Crossref.org
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