A novel computational approach for the prediction of networked transcription factors of aryl hydrocarbon-receptor-regulated genes

Molecular Pharmacology
Alexander KelJürgen Borlak

Abstract

A novel computational method based on a genetic algorithm was developed to study composite structure of promoters of coexpressed genes. Our method enabled an identification of combinations of multiple transcription factor binding sites regulating the concerted expression of genes. In this article, we study genes whose expression is regulated by a ligand-activated transcription factor, aryl hydrocarbon receptor (AhR), that mediates responses to a variety of toxins. AhR-mediated change in expression of AhR target genes was measured by oligonucleotide microarrays and by reverse transcription-polymerase chain reaction in human and rat hepatocytes. Promoters and long-distance regulatory regions (>10 kb) of AhR-responsive genes were analyzed by the genetic algorithm and a variety of other computational methods. Rules were established on the local oligonucleotide context in the flanks of the AhR binding sites, on the occurrence of clusters of AhR recognition elements, and on the presence in the promoters of specific combinations of multiple binding sites for the transcription factors cooperating in the AhR regulatory network. Our rules were applied to search for yet unknown Ah-receptor target genes. Experimental evidence is presented ...Continue Reading

References

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Jun 26, 2003·Nucleic Acids Research·A E KelE Wingender
Jul 23, 2003·Chemical Research in Toxicology·Stephen Safe, Mark Wormke

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Citations

Oct 24, 2006·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Christoph MoehleGerd Schmitz
Apr 12, 2007·Journal of Biosciences·Edgar WingenderAnatolij P Potapov
Jun 28, 2005·Nucleic Acids Research·Alessandro Di CaraEdward J Oakeley
Dec 31, 2005·Nucleic Acids Research·Xin ChenEdgar Wingender
Jul 20, 2007·Journal of Bioinformatics and Computational Biology·Stefan PoschIvo Grosse
Nov 23, 2006·BMC Bioinformatics·Alexdander KelEdgar Wingender
Jul 18, 2008·Experimental Dermatology·György ParaghGerd Schmitz
Dec 8, 2005·Birth Defects Research. Part A, Clinical and Molecular Teratology·Sara A CarneyRichard E Peterson
Nov 4, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·David C VolzSeth W Kullman
Feb 24, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tharu M FernandoCourtney E W Sulentic

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