histone deacetylases regulate gonadotropin-releasing hormone i gene expression via modulating otx2-driven transcriptional activity组蛋白去乙酰酶抑制剂调节促性腺激素释放激素通过调节otx2-driven我基因表达转录活动.pdfVIP

Histone Deacetylases Regulate Gonadotropin-Releasing Hormone I Gene Expression via Modulating Otx2-Driven Transcriptional Activity 1. 1. 1 2 1 1 1 1 Lu Gan , Pei-Yan Ni , Yan Ge , Yun-Fei Xiao , Chang-Yan Sun , Lin Deng , Wei Zhang , Si-Si Wu , 1 1 1,2 Ying Liu , Wei Jiang , Hong-Bo Xin * 1 Laboratory of Cardiovascular Diseases and Laboratory of Cellular and Molecular Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People’s Republic of China, 2 Institute of Translational Medicine, Nanchang University, Nanchang, People’s Republic of China Abstract Background: Precise coordination of the hypothalamic-pituitary-gonadal axis orchestrates the normal reproductive function. As a central regulator, the appropriate synthesis and secretion of gonadotropin-releasing hormone I (GnRH-I) from the hypothalamus is essential for the coordination. Recently, emerging evidence indicates that histone deacetylases (HDACs) play an important role in maintaining normal reproductive function. In this study, we identify the potential effects of HDACs on Gnrh1 gene transcription. Methodology/Principal Findings: Inhibition of HDACs activities by trichostatin A (TSA) and valproic acid (VPA) promptly and dramatically repressed transcription of Gnrh1 gene in the mouse immortalized mature GnRH neuronal cells GT1–7. The suppression was connected with a specific region of Gnrh1 gene promoter, which contains two consensus Otx2 binding sites. Otx2 has been known to activate the basal and also enhancer-driven transcription of Gnrh1 gene. The transcriptional activity of Otx2 is negatively modula