Identification of transcription factor and microRNA binding sites in responsible to fetal alcohol syndrome.
This is a first report, using our MotifModeler informatics program, to simultaneously identify transcription factor (TF) and microRNA (miRNA) binding sites from gene expression microarray data. Based on the assumption that gene expression is controlled by combinatorial effects of transcription factors binding in the 5'-upstream regulatory region and miRNAs binding in the 3'-untranslated region (3'-UTR), we developed a model for (1) predicting the most influential cis-acting elements under a given biological condition, and (2) estimating the effects of those elements on gene expression levels. The regulatory regions, TF and miRNA, which mediate the differential genes expression in fetal alcohol syndrome were unknown; microarray data from alcohol exposure paradigm was used. The model predicted strong inhibitory effects of 5' cis-acting elements and stimulatory effects of 3'-UTR under alcohol treatment. Current predictive model derived a key hypothesis for the first time a novel role of miRNAs in gene expression changes associated with abnormal mouse embryo development after alcohol exposure. This suggests that disturbance of miRNA functions may contribute to the alcohol-induced developmental deficiencies.
Wang
Guohua
G
Division of Biostatistics Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA. wang40@iupui.edu
Wang
Xin
X
Wang
Yadong
Y
Yang
Jack Y
JY
Li
Lang
L
Nephew
Kenneth P
KP
Edenberg
Howard J
HJ
Zhou
Feng C
FC
Liu
Yunlong
Y
D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology / Q000379:methods; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008957:Models, Genetic; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D035683:MicroRNAs; D014157:Transcription Factors