Potential binding sites for SF-1: Recognition by the SiteGA method, experimental verification, and search for new target genes

Abstract

The transcription factor SF-1 (steroidogenic factor 1) regulates the expression of the steroidogenesis genes, coordinates the development and function of the hypothalamic-pituitary-gonadal and adrenal systems, and plays an important role in the development and function of the reproductive system. SF-1 belongs to the superfamily of nuclear receptors and activates gene expression via binding as a monomer to DNA. The SiteGA method was developed for recognizing the binding sites for SF-1. The method utilizes a genetic algorithm and discriminant analysis to identify the context features of extended (93-bp) regions harboring the SF-1 sites in a training sample. Recognition of the SF-1 sites showed that the SiteGA method allows more reliable predictions as compared to the common weight matrix method. Experimental verification of 18 putative SF-1 sites predicted for the regulatory regions of the steroidogenesis genes showed that 15 (83%) of them did indeed interact with SF-1. The density of putative SF-1 sites was analyzed in the regulatory regions of genes from various functional groups, and new target genes of SF-1 were sought in the human genome. The potential targets of SF-1 include the genes coding for cytokine receptors, growth factor receptors, and proteins involved in the corresponding signal transduction pathways, as well as genes expressed in the epididymis. Expression of SF-1 in the epididymis was predicted and verified experimentally.