Literature DB >> 30259411

Intragenic Transcriptional cis-Antagonism Across SLC6A3.

Ying Zhao1,2, Jinlong Yu1, Juan Zhao1,3, Xiaowu Chen1,4, Nian Xiong1,5, Tao Wang5, Hong Qing3, Zhicheng Lin6.   

Abstract

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.

Entities:  

Keywords:  Epistasis; Genetic marker; Haplotype; Primate-specific; Transactivation

Mesh：

Substances：

Year:  2018        PMID： 30259411      PMCID： PMC6437023          DOI： 10.1007/s12035-018-1357-5

Source DB:  PubMed          Journal:  Mol Neurobiol        ISSN： 0893-7648            Impact factor:   5.590


  49 in total

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