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Identification of HIVEP2 as a dopaminergic transcription factor related to substance use disorders in rats and humans

J. Zhao, C. Chen, RL. Bell, H. Qing, Z. Lin,

. 2019 ; 9 (1) : 247. [pub] 20191004

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20025590

Grantová podpora
R24 AA015512 NIAAA NIH HHS - United States
R01 DA021409 NIDA NIH HHS - United States
U24 AA015512 NIAAA NIH HHS - United States
U01 AA013522 NIAAA NIH HHS - United States
U24 AA013522 NIAAA NIH HHS - United States

Playing an important role in the etiology of substance use disorder (SUD), dopamine (DA) neurons are subject to various regulations but transcriptional regulations are largely understudied. For the first time, we report here that the Human Immunodeficiency Virus Type I Enhancer Binding Protein 2 (HIVEP2) is a dopaminergic transcriptional regulator. HIVEP2 is expressed in both the cytoplasm and nuclei of DA neurons. Therein, HIVEP2 can target the intronic sequence GTGGCTTTCT of SLC6A3 and thereby activate the gene. In naive rats from the bi-directional selectively bred substance-preferring P vs -nonpreferring NP rat model of substance abuse vulnerability, increased gene activity in males was associated with the vulnerability, whereas decreased gene activity in the females was associated with the same vulnerability. In clinical subjects, extensive and significant HIVEP2-SLC6A3 interactions were observed for SUD. Collectively, HIVEP2-mediated transcriptional mechanisms are implicated in dopaminergic pathophysiology of SUD.

Citace poskytuje Crossref.org

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