Potential Binding Sites for SF-1:Recognition by the SiteGA Method,Experimental Verification, and Search for New Target Genes

摘要

The transcription factor SF-1(steroidogenic factor 1)regulates the expression of the steroidogene-sis genes,coordinates the development and function of the hypofhalamic-pituitary-gonadal and adrenal sys-tems,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 algo-rithm 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 var-ious 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.