Identification of HIVEP2 as a dopaminergic transcription factor related to substance use disorders in rats and humans
Jazyk angličtina Země Spojené státy americké Médium electronic
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
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
PubMed
31586043
PubMed Central
PMC6778090
DOI
10.1038/s41398-019-0573-8
PII: 10.1038/s41398-019-0573-8
Knihovny.cz E-zdroje
- MeSH
- buněčné jádro metabolismus MeSH
- DNA vazebné proteiny genetika metabolismus MeSH
- dopaminergní neurony metabolismus MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- myši inbrední C57BL MeSH
- poruchy spojené s užíváním psychoaktivních látek etiologie genetika MeSH
- proteiny přenášející dopamin přes plazmatickou membránu genetika metabolismus MeSH
- regulace genové exprese MeSH
- sexuální faktory MeSH
- transkripční faktory genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- DNA vazebné proteiny MeSH
- HIVEP2 protein, human MeSH Prohlížeč
- Hivep2 protein, mouse MeSH Prohlížeč
- Hivep2 protein, rat MeSH Prohlížeč
- proteiny přenášející dopamin přes plazmatickou membránu MeSH
- SLC6A3 protein, human MeSH Prohlížeč
- Slc6a3 protein, mouse MeSH Prohlížeč
- Slc6a3 protein, rat MeSH Prohlížeč
- transkripční faktory MeSH
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.
Laboratory of Psychiatric Genomics McLean Hospital Belmont MA 02478 USA
School of Life Science Beijing Institute of Technology 100081 Beijing China
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