Elucidation of regulatory mechanisms revealed by human promoter sequence analysis of genes co-expressed in forskolin-treated theca cells in PCOS

Abstract

Polycystic ovary syndrome (PCOS) is a reproductive endocrinopathy and is the most common cause of anovulatory infertility in women of reproductive age group. In PCOS research, there have been several reports which have shown the differential expression of genes from various tissue and cell types. However, little information can be gained about the regulation of these genes from the microarray data itself. Therefore, with the assumption that co-expression can also imply co-regulation in high-throughput gene expression studies, we investigated the role of various transcription factors by elucidating their binding sites (TFBSs) in these genes. For this purpose, a group of 40 genes altered in a forskolin-treated PCOS gene expression study in theca cells were analyzed using in silico tools. 2,000 bp of the upstream region were extracted from all these genes, and the PAINT suite of programs was used to identify over-represented TFBSs in these genes. We identified three different TFBSs which were over-represented as compared with a human promoter background model. These three transcription factors (TFs) are Oct, HFH, and neuron-restrictive silencing factor. Each of these three TFs and their compatible members can be implicated in the pathogenesis of PCOS, as described in detail in this article. These factors might reveal a new insight into the complex pathogenesis of PCOS especially with respect to cAMP pathway.