Abstract
Transcription factors are proteins that bind to DNA sequences to regulate gene transcription. The transcription factor binding sites are short DNA sequences (5–20 bp long) specifically bound by one or more transcription factors. The identification of transcription factor binding sites and prediction of their function continue to be challenging problems in computational biology. In this study, by integrating the DNase I hypersensitive sites with known position weight matrices in the TRANSFAC database, the transcription factor binding sites in gene regulatory region are identified. Based on the global gene expression patterns in cervical cancer HeLaS3 cell and HelaS3-ifnα4h cell (interferon treatment on HeLaS3 cell for 4 hours), we present a model-based computational approach to predict a set of transcription factors that potentially cause such differential gene expression. Significantly, 6 out 10 predicted functional factors, including IRF, IRF-2, IRF-9, IRF-1 and IRF-3, ICSBP, belong to interferon regulatory factor family and upregulate the gene expression levels responding to the interferon treatment. Another factor, ISGF-3, is also a transcriptional activator induced by interferon alpha. Using the different transcription factor binding sites selected criteria, the prediction result of our model is consistent. Our model demonstrated the potential to computationally identify the functional transcription factors in gene regulation.
Highlights
In molecular biology and genetics, transcription factors (TFs) are proteins that bind to DNA sequences thereby regulating the transcription of genetic information from DNA to messenger RNA [1]
We proposed a modified method that combined the DNase I hypersensitive sites with promoter regions to promote the accuracy of transcription factor binding sites (TFBSs) identification and recognize the regulatory function of transcription factors
We found that the binding sites of 26 transcription factors had more than 90% overlap and only 5 factors had less than 70% overlap with DNase I hypersensitive (DHS) sites
Summary
In molecular biology and genetics, transcription factors (TFs) are proteins that bind to DNA sequences thereby regulating the transcription of genetic information from DNA to messenger RNA [1]. Transcription factors bind to one or more sequence sites, which are called transcription factor binding sites (TFBSs), attaching to specific DNA sequences of the genes they regulate [2]. With the development of DNA microarrays and fast sequencing technique, many transcription factor binding sites have been identified by using experimental methods such as ChIPchip and ChIP-Seq [4,5,6]. Because these methods will consume many experiment materials and many TFs have no corresponding antibodies, biological experimental methods cannot identify all TFs in the genome. Many different computational methods have been proposed to search for additional members of a known transcription factor binding motif or discover novel transcription factor binding motifs
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