Deciphering the cis-regulatory elements of co-expressed genes in PCOS by in silico analysis.
In recent times, the focus of research in polycystic ovary syndrome (PCOS) has shifted from candidate gene(s) approach to whole genome analysis for deciphering its molecular pathophysiology. In this regard, several microarray studies have been published, showing differential expression of genes between normal and PCOS states. Co-expression of genes as obtained in microarray experiments can also imply co-regulation at the transcriptional level by various transcription factors. In order to identify such transcription factors, the in silico elucidation of Transcription Factor Binding Sites (TFBS) is emerging as an important tool. With this hypothesis, we looked for TFBS over-representation in a PCOS microarray gene set (n=130) using in silico tools. We extracted 1000 bps upstream and 200 bps downstream regions from all these genes and identified 4 different TFBS, which were over-represented as compared to a human promoter background model. These four transcription factors are Staf, E47, CCAAT and CRE-BP1/c-jun. The role of these transcription factors and their compatible members in PCOS pathophysiology is described in details in the text. The factors might provide a novel insight into the pathophysiology of PCOS.
Department of Molecular Endocrinology, National Institute for Research in Reproductive Health (ICMR), Mumbai-400012, Parel, India.
Chiradeep
C
Sarkar
Anurupa
A
Maitra
D051698:Activating Transcription Factor 2 / Q000235:genetics; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D005260:Female; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D051820:TCF Transcription Factors / Q000737:chemistry / Q000235:genetics; D013799:Theca Cells; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics; D058125:Transcription Factor 7-Like 1 Protein
D051698:Activating Transcription Factor 2; D004268:DNA-Binding Proteins; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; C114253:ZNF143 protein, human