Promoters of the genes encoding the transcription factors regulating the cytokine gene expression in macrophages contain putative binding sites for aryl hydrocarbon receptor.
The computer system SITECON was used to study the regulatory regions in the transcription factor genes expressed in the activated macrophage and the genes of the proteins mediating the macrophage involvement in the immune response. Dioxin responsive elements (DREs), the specific sites responsible for expression regulation of the genes involved in the cell response to dioxin, were found in these gene regions. Thus, the role of dioxin in activity regulation of the genes involved in development of the immune response can be regulated both directly, by the transcription complex containing dioxin as a ligand, and indirectly, via intrinsic transcription factors.The double regulation, via DRE and the binding sites for the corresponding transcription factors in the promoter regions of macrophage genes, and the interregulation of the genes providing for the immune response allow the system to rapidly respond to a provocative agent (xenobiotic) and finely tune its function.
Furman
Dagmara P
DP
Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, pr. Lavrentieva 10, Novosibirsk 630090, Russia. furman@bionet.nsc.ru
Oshchepkova
Eugenia A
EA
Oshchepkov
Dmitry Yu
DY
Shamanina
Marina Yu
MY
Mordvinov
Viatcheslav A
VA
D001665:Binding Sites / Q000187:drug effects; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D016207:Cytokines / Q000737:chemistry / Q000235:genetics*; D004147:Dioxins / Q000737:chemistry / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D008024:Ligands; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics*; D018336:Receptors, Aryl Hydrocarbon / Q000737:chemistry / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*
D016207:Cytokines; D004147:Dioxins; D008024:Ligands; D018336:Receptors, Aryl Hydrocarbon