CCAAT/enhancer-binding protein {beta} (C/EBP{beta}) mediates progesterone production through transcriptional regulation in cooperation with steroidogenic factor 1 (SF-1)

A transcription factor, steroidogenic factor 1 (SF-1), is a master regulator for steroidogenesis. Previously, we have found that SF-1 induces the differentiation of mesenchymal stem cells into steroidogenic cells. To elucidate the molecular mechanisms of SF-1-mediated functions, we attempted to identify protein components of the SF-1 nuclear protein complex in differentiated cells. SF-1 immunoaffinity chromatography followed by MS/MS analysis was performed, and 24 proteins were identified. Among these proteins, we focused on CCAAT/enhancer-binding protein β (C/EBPβ), which is an essential transcription factor for ovulation and luteinization, as the transcriptional mechanisms of C/EBPβ working together with SF-1 are poorly understood. C/EBPβ knockdown attenuated cAMP-induced progesterone production in granulosa tumor-derived KGN cells by altering STAR, CYP11A1 and HSD3B2 expression. EMSA and ChIP assays revealed novel C/EBPβ binding sites in the upstream regions of the HSD3B2 and CYP11A1 genes. These interactions were enhanced by cAMP stimulation. Luciferase assays showed that C/EBPβ-responsive regions were found in each promoter and C/EBPβ is involved in the cAMP-induced transcriptional activity of these genes together with SF-1. These results indicate that C/EBPβ is an important mediator of progesterone production by working together with SF-1, especially under tropic hormone-stimulated condition.
Source: BJ Gene - Category: Biochemistry Authors: Tags: BJ Gene Source Type: research