Identification of transcription factor and microRNA binding sites in responsible to fetal alcohol syndrome

Identification of transcription factor and microRNA binding sites in responsible to fetal alcohol syndrome

20 March 2008 | Guohua Wang, Xin Wang, Yadong Wang, Jack Y Yang, Lang Li, Kenneth P Nephew, Howard J Edenberg, Feng C Zhou, Yunlong Liu
This study presents a novel method using the MotifModeler program to simultaneously identify transcription factor (TF) and microRNA (miRNA) binding sites from gene expression microarray data. The approach is based on the assumption that gene expression is regulated by the combined effects of TFs in the 5'-upstream regulatory region and miRNAs in the 3'-untranslated region (3'-UTR). The model predicts the most influential cis-acting elements under specific biological conditions and estimates their effects on gene expression levels. The study uses microarray data from an alcohol exposure paradigm to analyze gene expression changes in fetal alcohol syndrome (FAS) mouse embryos. The model predicted strong inhibitory effects of 5' cis-acting elements and stimulatory effects of 3'-UTR elements under alcohol treatment. This suggests that miRNA dysfunction may contribute to alcohol-induced developmental deficiencies. The study introduces a model-based approach to identify potential TF and miRNA binding sites from microarray-derived gene expression data and genomic DNA sequences. The method involves analyzing regulatory sequences in both the 5'-proximal flanking region and the 3'-UTR of differentially expressed genes. The model uses a mathematical framework to estimate the functional levels of TF and miRNA binding sites and assess their impact on gene expression. The results show that many TF and miRNA binding sites are significantly affected by alcohol treatment, with some showing inhibitory and others stimulatory effects. The study also identifies several TFs and miRNAs that are associated with developmental deficits in FAS, including those involved in growth, neural specification, hemopoiesis, and apoptosis. The findings suggest that miRNAs play a novel role in gene expression changes associated with abnormal mouse embryo development after alcohol exposure. The study highlights the importance of integrating TF and miRNA regulatory mechanisms in understanding global gene expression patterns.This study presents a novel method using the MotifModeler program to simultaneously identify transcription factor (TF) and microRNA (miRNA) binding sites from gene expression microarray data. The approach is based on the assumption that gene expression is regulated by the combined effects of TFs in the 5'-upstream regulatory region and miRNAs in the 3'-untranslated region (3'-UTR). The model predicts the most influential cis-acting elements under specific biological conditions and estimates their effects on gene expression levels. The study uses microarray data from an alcohol exposure paradigm to analyze gene expression changes in fetal alcohol syndrome (FAS) mouse embryos. The model predicted strong inhibitory effects of 5' cis-acting elements and stimulatory effects of 3'-UTR elements under alcohol treatment. This suggests that miRNA dysfunction may contribute to alcohol-induced developmental deficiencies. The study introduces a model-based approach to identify potential TF and miRNA binding sites from microarray-derived gene expression data and genomic DNA sequences. The method involves analyzing regulatory sequences in both the 5'-proximal flanking region and the 3'-UTR of differentially expressed genes. The model uses a mathematical framework to estimate the functional levels of TF and miRNA binding sites and assess their impact on gene expression. The results show that many TF and miRNA binding sites are significantly affected by alcohol treatment, with some showing inhibitory and others stimulatory effects. The study also identifies several TFs and miRNAs that are associated with developmental deficits in FAS, including those involved in growth, neural specification, hemopoiesis, and apoptosis. The findings suggest that miRNAs play a novel role in gene expression changes associated with abnormal mouse embryo development after alcohol exposure. The study highlights the importance of integrating TF and miRNA regulatory mechanisms in understanding global gene expression patterns.
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[slides and audio] BMC Genomics BioMed Central