Computer-assisted identification of cell cycle-related genes: new targets for E2F transcription factors

Kel, A. E., Kel-Margoulis, O. V., Farnham, P. J., Bartley, S. M., Wingender, E., Zhang, M. Q. (May 2001) Computer-assisted identification of cell cycle-related genes: new targets for E2F transcription factors. Journal of Molecular Biology, 309 (1). pp. 99-120. ISSN 0022-2836

URL: http://www.ncbi.nlm.nih.gov/pubmed/11491305

DOI: 10.1006/jmbi.2001.4650

Abstract

The processes that take place during development and differentiation are directed through coordinated regulation of expression of a large number of genes. One such gene regulatory network provides cell cycle control in eukaryotic organisms. Ln this work, we have studied the structural features of the 5' regulatory regions of cell cycle-related genes. We developed a new method for identifying composite substructures (modules) in regulatory regions of genes consisting of a binding site for a key transcription factor and additional contextual motifs: potential targets for other transcription factors that may synergistically regulate gene transcription. Applying this method to cell cycle-related promoters, we created a program for context-specific identification of binding sites for transcription factors of the E2F family which are key regulators of the cell cycle. We found that E2F composite modules are found at a high frequency and in close proximity to the start of transcription in cell cycle-related promoters in comparison with other promoters. Using this information, we then searched for E2F sites in genomic sequences with the goal of identifying new genes which play important roles in controlling cell proliferation, differentiation and apoptosis. Using a chromatin immunoprecipitation assay, we then experimentally verified the binding of E2F in vivo to the promoters predicted by the computer-assisted methods. Our identification of new E2F target genes provides new insight into gene regulatory networks and provides a framework for continued analysis of the role of contextual promoter features in transcriptional regulation. The tools described are available at http://compel.bionet.nsc.ru/FunSite/SiteScan.html

Item Type:	Paper
Uncontrolled Keywords:	cell cycle E2F transcription factors computer-associated prediction composite elements weight matrix DIHYDROFOLATE-REDUCTASE PROMOTER TUMOR-SUPPRESSOR PROTEIN DNA-BINDING SITES GROWTH-REGULATION IN-VIVO ACTIVATION EXPRESSION REPRESSION ELEMENTS FAMILY
Subjects:	bioinformatics > genomics and proteomics > computers bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell cycle bioinformatics > genomics and proteomics > computers > computer software bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Zhang, Michael Q.
Communities:	CSHL labs > Zhang lab
Depositing User:	Matt Covey
Date:	May 2001
Date Deposited:	22 Jan 2014 16:52
Last Modified:	22 Jan 2014 16:52
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/29257

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