This Article Full Text Full Text (PDF) Supplemental Research Data All Versions of this Article: gr.4303406v1 16/3/405    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chang, L.-W. Articles by Stormo, G. D. Search for Related Content PubMed PubMed Citation Articles by Chang, L.-W. Articles by Stormo, G. D. Social Bookmarking                   What's this?

Methods

A systematic model to predict transcriptional regulatory mechanisms based on overrepresentation of transcription factor binding profiles

¹ Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA ² Department of Biomedical Engineering, Washington University, St. Louis, Missouri 63130, USA ³ Department of Pathology and Immunology, Division of Laboratory Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA

An important aspect of understanding a biological pathway is to delineate the transcriptional regulatory mechanisms of the genes involved. Two important tasks are often encountered when studying transcription regulation, i.e., (1) the identification of common transcriptional regulators of a set of coexpressed genes; (2) the identification of genes that are regulated by one or several transcription factors. In this study, a systematic and statistical approach was taken to accomplish these tasks by establishing an integrated model considering all of the promoters and characterized transcription factors (TFs) in the genome. A promoter analysis pipeline (PAP) was developed to implement this approach. PAP was tested using coregulated gene clusters collected from the literature. In most test cases, PAP identified the transcription regulators of the input genes accurately. When compared with chromatin immunoprecipitation experiment data, PAP's predictions are consistent with the experimental observations. When PAP was used to analyze one published expression-profiling data set and two novel coregulated gene sets, PAP was able to generate biologically meaningful hypotheses. Therefore, by taking a systematic approach of considering all promoters and characterized TFs in our model, we were able to make more reliable predictions about the regulation of gene expression in mammalian organisms.

Article published online ahead of print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.4303406.

⁴ Corresponding author.
E-mail stormo{at}genetics.wustl.edu; fax (314) 362-7855.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Sinha, A. S. Adler, Y. Field, H. Y. Chang, and E. Segal Systematic functional characterization of cis-regulatory motifs in human core promoters Genome Res., March 1, 2008; 18(3): 477 - 488. [Abstract] [Full Text] [PDF]

				S. R. Davies, L.-W. Chang, D. Patra, X. Xing, K. Posey, J. Hecht, G. D. Stormo, and L. J. Sandell Computational identification and functional validation of regulatory motifs in cartilage-expressed genes Genome Res., October 1, 2007; 17(10): 1438 - 1447. [Abstract] [Full Text] [PDF]

				L.-W. Chang, B. R. Fontaine, G. D. Stormo, and R. Nagarajan PAP: a comprehensive workbench for mammalian transcriptional regulatory sequence analysis Nucleic Acids Res., July 13, 2007; 35(suppl_2): W238 - W244. [Abstract] [Full Text] [PDF]

				N. A. Kolchanov, T. I. Merkulova, E. V. Ignatieva, E. A. Ananko, D. Yu. Oshchepkov, V. G. Levitsky, G. V. Vasiliev, N. V. Klimova, V. M. Merkulov, and T. C. Hodgman Combined experimental and computational approaches to study the regulatory elements in eukaryotic genes Brief Bioinform, July 12, 2007; (2007) bbm027v1. [Abstract] [Full Text] [PDF]

				X. Wang, D. J. Tomso, B. N. Chorley, H.-Y. Cho, V. G. Cheung, S. R. Kleeberger, and D. A. Bell Identification of polymorphic antioxidant response elements in the human genome Hum. Mol. Genet., May 15, 2007; 16(10): 1188 - 1200. [Abstract] [Full Text] [PDF]