He Chengqiang, Ding Naizheng, Kang Jie
College of Life Science, Shandong Normal University, Jinan 250014, China.
Acta Biochim Biophys Sin (Shanghai). 2008 Mar;40(3):253-60. doi: 10.1111/j.1745-7270.2008.00395.x.
Germ cell nuclear factor (GCNF) is a transcription factor that can repress gene transcription and plays an important role during spermatogenesis. Peroxisome proliferator-activated receptor delta (PPARdelta) is a nuclear hormone receptor belonging to the steroid receptor superfamily. It can activate the expression of many genes, including those involved in lipid metabolism. In this report, we showed that GCNF specifically interacts with PPARdelta promoter. Overexpression of GCNF in African green monkey SV40-transformed kidney fibroblast COS7 cells and mouse embryo fibroblast NIH 3T3 cells represses the activity of PPARdelta promoter. The mutation of GCNF response element in PPARdelta promoter relieves the repression in NIH 3T3 cells and mouse testis. Moreover, we showed that GCNF in nuclear extracts of mouse testis is able to bind to PPARdelta promoter directly. We also found that GCNF and PPARdelta mRNA were expressed with different patterns in mouse testis by in situ hybridization. These results suggested that GCNF might be a negative regulator of PPARdelta gene expression through its direct interaction with PPARdelta promoter in mouse testis.
生殖细胞核因子（GCNF）是一种转录因子，可抑制基因转录，并在精子发生过程中发挥重要作用。过氧化物酶体增殖物激活受体δ（PPARδ）是属于类固醇受体超家族的核激素受体。它可激活许多基因的表达，包括那些参与脂质代谢的基因。在本报告中，我们表明GCNF与PPARδ启动子特异性相互作用。在非洲绿猴SV40转化的肾成纤维细胞COS7细胞和小鼠胚胎成纤维细胞NIH 3T3细胞中过表达GCNF可抑制PPARδ启动子的活性。PPARδ启动子中GCNF反应元件的突变可减轻NIH 3T3细胞和小鼠睾丸中的抑制作用。此外，我们表明小鼠睾丸核提取物中的GCNF能够直接与PPARδ启动子结合。我们还通过原位杂交发现GCNF和PPARδ mRNA在小鼠睾丸中以不同模式表达。这些结果表明，GCNF可能通过其与小鼠睾丸中PPARδ启动子的直接相互作用而成为PPARδ基因表达的负调节因子。
