In silico Analysis of Downstream Target Genes of Transcription Factors

생명정보학을 이용한 전사인자의 하위표적유전자 분석에 관한 연구

  • Hwang, Sang-Joon (Graduate School of Life Science and Biotechnology, Pochon CHA University College of Medicine) ;
  • Chun, Sang-Young (School of Biological Sciences and Technology, chonnam National University) ;
  • Lee, Kyung-Ah (Graduate School of Life Science and Biotechnology, Pochon CHA University College of Medicine)
  • 황상준 (포천중문의과대학교 생명과학전문대학원) ;
  • 전상영 (전남대학교 생명과학기술학부) ;
  • 이경아 (포천중문의과대학교 생명과학전문대학원)
  • Published : 2006.06.30

Abstract

Objective: In the previous study, we complied the differentially expressed genes during early folliculogenesis. 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 & 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 searches 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.

Acknowledgement

Supported by : 한국학술진흥재단

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