Beyond the Identification of Transcribed Sequences:
Functional, Evolutionary and Expression Analysis
12th International Workshop
October 25-28, 2002
Washington, DC


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Computational and In Vitro Analysis of Destabilized DNA Regions in the Interferon Gene Cluster: The Potential of Predicting Functional Gene Domains

S. Goetze, A. Gluch, C. Benham and J. Bode
GBF- German Research Center for Biotechnology/Epigenetic Regulation, Mascheroder Weg 1, D-38124 Braunschweig; GERMANY
Telephone: +49 531 6181 251
Fax: +49 531 6181 262
Email: juergenbode@gbf.de

Recent evidence adds support to a traditional concept according to which the eukaryotic nucleus is organized into functional domains by scaffold or matrix attachment regions (S/MARs). These regions have previously been predicted to have a high potential for stress induced duplex destabilization (SIDD). Here we report the parallel results of binding (re-association) and computational SIDD analyses for regions within the human interferon gene cluster on the short arm of chromosome 9 (9p22). To verify and further refine the biomathematical methods, we focus on a 10 kb region in the cluster with the pseudogene IFNWP18 and the interferon alpha genes IFNA10 and IFNA7. In a series of S/MAR binding assays we investigate the promoter and termination regions, and additional attachment sequences that were detected in the SIDD profile. The promoters of the IFNA10 and the IFNA7 genes have a moderate ~20% binding affinity to the nuclear matrix; the termination sequences show stronger association (70-80%) under our standardized conditions. No comparable destabilized elements were detected flanking the IFNWP18 pseudogene, suggesting that selective pressure acts on the physicochemical properties detected here. In extended, non-coding regions a striking periodicity is found of rather restricted SIDD minima with scaffold binding potential. By various criteria, the underlying sequences represent a new class of S/MARs , thought to be involved in a higher level organization of the genome. Together, these data emphasize the relevance of SIDD calculations as a valid approach for the localization of structural, regulatory and coding regions in the eukaryotic genome. New data show that they have the added potential to cover DNAse I hypersensitive and fragile sites that are either of regulatory relevance or the molecular cause of genome instability or the insertion of foreign DNA. This concept will be supported by halo-FISH analyses.



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