Identification of novel steroidogenic factor 1 (SF-1)-target genes and components of the SF-1 nuclear complex

• Coordinated expression of all hGSTA family is regulated by SF-1 via altering higher-order chromatin structure.
• Human GSTA1-1 and A3-3 work as the steroid metabolic enzyme.
• ALAS1 and FDXR are SF-1-target genes and participate in steroidogenesis.
• C/EBPβ is one of the components of the SF-1 nuclear protein complex and an important mediator of progesterone production by working with SF-1.

Steroidogenic factor 1 (SF-1) is a master regulator of adrenal and reproductive development and function. Although SF-1 was identified as a transcriptional regulator for steroid metabolic enzymes, it has been shown that SF-1 also regulates other genes that are involved in various cellular processes. Previously, we showed that introduction of SF-1 into mesenchymal stem cells resulted in the differentiation of these cells to the steroidogenic lineage. By using this method of differentiation, we performed comprehensive analyses to identify the novel SF-1-target genes and components of the SF-1 nuclear complex. Genome-wide analyses with promoter tiling array and DNA microarray identified 10 genes as novel SF-1-target genes including glutathione S-transferase A family, 5-aminolevulinic acid synthase 1 and ferredoxin reductase. Using SF-1 immuno-affinity chromatography of nuclear proteins followed by MS/MS analysis, we identified 24 proteins including CCAAT/enhancer-binding protein β as components of SF-1 nuclear complex. In this review, we will describe novel roles of the newly identified genes for steroidogenesis.