Biopolymers and cell. 2009; 25 (5): 398 - 402

Identification of gene targets of ISGF-3 transcription factor

B. T. Tokovenko, O. O. Dragushchenko, A. V. Kuklin, M. Yu. Obolenskaya

Institute of molecular biology and genetics NAS of Ukraine
150, Zabolotnogo Str, Kyiv Ukraine, 03680

Aim. Transcription factor ISGF-3 is activated as a result of the signal transduction from IFNα via the dominating Jak-STAT pathway. The discovery of ISGF-3 binding sites will assist in identifying genes of primary response to IFNα. Methods. COTRASIF is a web-based tool for the genome-wide identification of the evolutionary-conservative regulatory sites in the promoters of eukaryotic genes. It offers 3 search methods: based on position-weight matrices (PWM), hybrid method based on hidden Markov models (PWM-HMM), and phylogenetic footprinting. Results. We have demonstrated that PWM-HMM method has higher search specificity, and used this method to identify the gene targets of ISGF-3 transcription factor. After applying phylogenetic foot-printing, we have obtained a list of 162 genes of putative primary response to IFNα. The reliability metrics to these gene targets has been developed and applied. Conclusions. Based on the search results, Gene Ontology over-representation analysis, and reliability metrics, we have identified 24 rat protein-coding genes as promising targets for further studies on the primary response to IFNα.

Keywords: interferon, ISGF-3, COTRASIF, IFNα.