Korean J Fertil Steril.  2006 Jun;33(2):125-132.

In silico Analysis of Downstream Target Genes of Transcription Factors

• Hwang SJ
• Chun SY
• Lee KA

Abstract

OBJECTIVE
In the previous study, we compiled the differentially expressed genes during early folliculogenesis.1 Objective of the present study was to identify downstream target genes of transcription factors (TFs) using bioinformatics for selecting the target TFs among the gene lists for further functional analysis. MATERIALS AND METHODS: By using bioinformatics tools, constituent domains were identified from database searches using Gene Ontology, MGI, and Entrez Gene. Downstream target proteins/genes of each TF were identified from database searches using TF database (TRANSFAC(R) 6.0) and eukaryotic promoter database (EPD).
RESULTS
DNA binding and trans-activation domains of all TFs listed previously were identified, and the list of downstream target proteins/genes was obtained from searche of TF database and promoter database. Based on the known function of identified downstream genes and the domains, 3 (HNF4, PPARg, and TBX2) out of 26 TFs were selected for further functional analysis. The genes of wee1-like protein kinase and p21WAF1 (cdk inhibitor) were identified as potential downstream target genes of HNF4 and TBX2, respectively. PPARg, through protein-protein interaction with other protein partners, acts as a transcription regulator of genes of EGFR, p21WAF1, cycD1, p53, and VEGF. Among the selected 3 TFs, further study is in progress for HNF4 and TBX2, since wee1-like protein kinase and cdk inhibitor may involved in regulating maturation promoting factor (MPF) activity during early folliculogenesis.
CONCLUSIONS
Approach used in the present study, in silico analysis of downstream target genes, was useful for analyzing list of TFs obtained from high-throughput cDNA microarray study. To verify its binding and functions of the selected TFs in early folliculogenesis, EMSA and further relevant characterizations are under investigation.

Keyword

Folliculogenesis; Bioinformatics; Transcription factor; Binding element; Downstream target gene

MeSH Terms

Computational Biology
Computer Simulation*
DNA
Gene Ontology
Maturation-Promoting Factor
Oligonucleotide Array Sequence Analysis
Protein Kinases
Transcription Factors*
Vascular Endothelial Growth Factor A
DNA
Maturation-Promoting Factor
Protein Kinases
Transcription Factors
Vascular Endothelial Growth Factor A