![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication April 29, 2004.
Revised August 26, 2004.
Accepted for publication August 26, 2004.
A novel computational method based on a genetic algorithm was developed to study composite structure of promoters of co-expressed genes. Our method enabled an identification of combinations of multiple transcription factor binding sites regulating the concerted expression of genes. In this paper we study genes whose expression is regulated by a ligand-activated transcription factor AhR (aryl hydrocarbon receptor) that mediates responses to a variety of toxins. AhR mediated change in expression of Ahr target genes was measured by oligo microarrays and by RT-PCR in human and rat hepatocytes. Promoters and long distance regulatory regions (>10 kb) of AhR responsive genes were analysed by the genetic algorithm and a variety of other computational methods. Rules were established on the local oligonucleotide context in the flanks of the Ah-receptor 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 co-operating in the AhR regulatory network. Our rules were applied to search for yet unknown Ah-receptor target genes. Experimental evidence is presented to demonstrate high fidelity of this novel in silico approach.
Key words:
Comparative genome analyses, Ah receptor, Genetics
This article has been cited by other articles:
|
|
 |
|
  E. Wingender The TRANSFAC project as an example of framework technology that supports the analysis of genomic regulation Brief Bioinform, July 1, 2008; 9(4): 326 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Wu, L. Zhang, M. S. Hoagland, and H. I. Swanson Lack of the Aryl Hydrocarbon Receptor Leads to Impaired Activation of AKT/Protein Kinase B and Enhanced Sensitivity to Apoptosis Induced via the Intrinsic Pathway J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 448 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Waleev, D. Shtokalo, T. Konovalova, N. Voss, E. Cheremushkin, P. Stegmaier, O. Kel-Margoulis, E. Wingender, and A. Kel Composite Module Analyst: identification of transcription factor binding site combinations using genetic algorithm. Nucleic Acids Res., July 1, 2006; 34(Web Server issue): W541 - W545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kel, T. Konovalova, T. Waleev, E. Cheremushkin, O. Kel-Margoulis, and E. Wingender Composite Module Analyst: a fitness-based tool for identification of transcription factor binding site combinations Bioinformatics, May 15, 2006; 22(10): 1190 - 1197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Volz, D. E. Hinton, J. M. Law, and S. W. Kullman Dynamic Gene Expression Changes Precede Dioxin-Induced Liver Pathogenesis in Medaka Fish Toxicol. Sci., February 1, 2006; 89(2): 524 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, J.-m. Wu, K. Hornischer, A. Kel, and E. Wingender TiProD: the Tissue-specific Promoter Database Nucleic Acids Res., January 1, 2006; 34(suppl_1): D104 - D107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Di Cara, K. Schmidt, B. A. Hemmings, and E. J. Oakeley PromoterPlot: a graphical display of promoter similarities by pattern recognition Nucleic Acids Res., July 1, 2005; 33(suppl_2): W423 - W426. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
