Prediction and experimental validation of novel STAT3 target genes in human cancer cells.
The comprehensive identification of functional transcription factor binding sites (TFBSs) is an important step in understanding complex transcriptional regulatory networks. This study presents a motif-based comparative approach, STAT-Finder, for identifying functional DNA binding sites of STAT3 transcription factor. STAT-Finder combines STAT-Scanner, which was designed to predict functional STAT TFBSs with improved sensitivity, and a motif-based alignment to minimize false positive prediction rates. Using two reference sets containing promoter sequences of known STAT3 target genes, STAT-Finder identified functional STAT3 TFBSs with enhanced prediction efficiency and sensitivity relative to other conventional TFBS prediction tools. In addition, STAT-Finder identified novel STAT3 target genes among a group of genes that are over-expressed in human cancer cells. The binding of STAT3 to the predicted TFBSs was also experimentally confirmed through chromatin immunoprecipitation. Our proposed method provides a systematic approach to the prediction of functional TFBSs that can be applied to other TFs.
Oh
Young Min
YM
Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea.
Kim
Jong Kyoung
JK
Choi
Yongwook
Y
Choi
Seungjin
S
Yoo
Joo-Yeon
JY
D000465:Algorithms; D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D051379:Mice; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors