Computer-assisted identification of cell cycle-related genes

New targets for E2F transcription factors

Alexander E. Kel, Olga V. Kel-Margoulis, Peggy J. Farnham, Stephanie M. Bartley, Edgar Wingender, Michael Q. Zhang

Research output: Contribution to journalArticle

152 Citations (Scopus)

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. In 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.

Original languageEnglish (US)
Pages (from-to)99-120
Number of pages22
JournalJournal of Molecular Biology
Volume309
Issue number1
DOIs
StatePublished - May 25 2001
Externally publishedYes

Fingerprint

E2F Transcription Factors
cdc Genes
Cell Cycle
Gene Regulatory Networks
Nucleic Acid Regulatory Sequences
Genes
Transcription Factors
Binding Sites
Chromatin Immunoprecipitation
Regulator Genes
Cell Cycle Checkpoints
Cell Differentiation
Cell Proliferation
Apoptosis

Keywords

  • Cell cycle
  • Composite elements
  • Computer-associated prediction
  • E2F transcription factors
  • Weight matrix

ASJC Scopus subject areas

  • Virology

Cite this

Kel, A. E., Kel-Margoulis, O. V., Farnham, P. J., Bartley, S. M., Wingender, E., & Zhang, M. Q. (2001). Computer-assisted identification of cell cycle-related genes: New targets for E2F transcription factors. Journal of Molecular Biology, 309(1), 99-120. https://doi.org/10.1006/jmbi.2001.4650

Computer-assisted identification of cell cycle-related genes : New targets for E2F transcription factors. / Kel, Alexander E.; Kel-Margoulis, Olga V.; Farnham, Peggy J.; Bartley, Stephanie M.; Wingender, Edgar; Zhang, Michael Q.

In: Journal of Molecular Biology, Vol. 309, No. 1, 25.05.2001, p. 99-120.

Research output: Contribution to journalArticle

Kel, AE, Kel-Margoulis, OV, Farnham, PJ, Bartley, SM, Wingender, E & Zhang, MQ 2001, 'Computer-assisted identification of cell cycle-related genes: New targets for E2F transcription factors', Journal of Molecular Biology, vol. 309, no. 1, pp. 99-120. https://doi.org/10.1006/jmbi.2001.4650
Kel, Alexander E. ; Kel-Margoulis, Olga V. ; Farnham, Peggy J. ; Bartley, Stephanie M. ; Wingender, Edgar ; Zhang, Michael Q. / Computer-assisted identification of cell cycle-related genes : New targets for E2F transcription factors. In: Journal of Molecular Biology. 2001 ; Vol. 309, No. 1. pp. 99-120.
@article{21a1f1a5eb734e268542d13d90debd13,
title = "Computer-assisted identification of cell cycle-related genes: New targets for E2F transcription factors",
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. In 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.",
keywords = "Cell cycle, Composite elements, Computer-associated prediction, E2F transcription factors, Weight matrix",
author = "Kel, {Alexander E.} and Kel-Margoulis, {Olga V.} and Farnham, {Peggy J.} and Bartley, {Stephanie M.} and Edgar Wingender and Zhang, {Michael Q.}",
year = "2001",
month = "5",
day = "25",
doi = "10.1006/jmbi.2001.4650",
language = "English (US)",
volume = "309",
pages = "99--120",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Computer-assisted identification of cell cycle-related genes

T2 - New targets for E2F transcription factors

AU - Kel, Alexander E.

AU - Kel-Margoulis, Olga V.

AU - Farnham, Peggy J.

AU - Bartley, Stephanie M.

AU - Wingender, Edgar

AU - Zhang, Michael Q.

PY - 2001/5/25

Y1 - 2001/5/25

N2 - 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. In 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.

AB - 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. In 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.

KW - Cell cycle

KW - Composite elements

KW - Computer-associated prediction

KW - E2F transcription factors

KW - Weight matrix

UR - http://www.scopus.com/inward/record.url?scp=0035946917&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035946917&partnerID=8YFLogxK

U2 - 10.1006/jmbi.2001.4650

DO - 10.1006/jmbi.2001.4650

M3 - Article

VL - 309

SP - 99

EP - 120

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 1

ER -