Germ cell nuclear factor directly represses the transcription of peroxisome proliferator-activated receptor delta gene.

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.