Nicotine Suppressed Fetal Adrenal StAR Expression via YY1 Mediated-Histone Deacetylation Modification Mechanism.
Steroidogenic acute regulatory (StAR) protein plays a pivotal role in steroidogenesis. Previously, we have demonstrated that prenatal nicotine exposure suppressed fetal adrenal steroidogenesis via steroidogenic factor 1 deacetylation. This study further explored the potential role of the transcriptional repressor Yin Yang 1 (YY1) in nicotine-mediated StAR inhibition. Nicotine was subcutaneously administered (1.0 mg/kg) to pregnant rats twice per day and NCI-H295A cells were treated with nicotine. StAR and YY1 expression were analyzed by real-time PCR, immunohistochemistry, and Western blotting. Histone modifications and the interactions between the YY1 and StAR promoter were assessed using chromatin immunoprecipitation (ChIP). Prenatal nicotine exposure increased YY1 expression and suppressed StAR expression. ChIP assay showed that there was a decreasing trend for histone acetylation at the StAR promoter in fetal adrenal glands, whereas H3 acetyl-K14 at the YY1 promoter presented an increasing trend following nicotine exposure. Furthermore, in nicotine-treated NCI-H295A cells, nicotine enhanced YY1 expression and inhibited StAR expression. ChIP assay showed that histone acetylation decreased at the StAR promoter in NCI-H295A cells and that the interaction between the YY1 and StAR promoter increased. These data indicated that YY1-medicated histone deacetylation modification in StAR promoters might play an important role in the inhibitory effect of nicotine on StAR expression.
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China. zifanqie_00@126.com.|Department of Pharmacology, Medical School of Yangtze University, Jingzhou 434000, China. zifanqie_00@126.com.
Lian
L
Liu
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China. wangjianfay@163.com.
Jian-Fei
JF
Wang
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China. fanjcn@163.com.
Jie
J
Fan
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China. raoyisong@whu.edu.cn.
Yi-Song
YS
Rao
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China. liufang1020@126.com.
Fang
F
Liu
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China. yanyoue@whu.edu.cn.
You-E
YE
Yan
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China. wanghui19@whu.edu.cn.
Hui
H
Wang
D000107:Acetylation; D000311:Adrenal Glands / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D009538:Nicotine / Q000494:pharmacology* / Q000633:toxicity; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D050986:YY1 Transcription Factor / Q000378:metabolism*; D000098682:Steroidogenic Acute Regulatory Protein
D006657:Histones; D010750:Phosphoproteins; D050986:YY1 Transcription Factor; D000098682:Steroidogenic Acute Regulatory Protein; D009538:Nicotine
Yin Yang 1 (YY1); fetal adrenal; histone deacetylation; nicotine; steroidogenic acute regulatory (StAR)