Scaffold-Associated Regions in the Human Type I Interferon Gene Cluster on the Short Arm of Chromosome 9

Scaffold-associated regions (SARs) function at the level of modeling or shaping the chromatin of DNA into loop domains. We have mapped 36 SARs in the human type I interferon ( IFN ) gene complex on chromosome 9, band p21-22, to examine the overall structure of this gene complex. A total of 29 strong SARs and 7 weak SARs were mapped to the flanking regions of the different interferon genes. Twenty-two strong SARs mapped to the flanking regions of 13 interferon ( IFNA ) α genes; 2 strong SARs mapped to one interferon ω ( IFNW ) gene; 2 strong SARs mapped to one interferon α pseudogene ( IFNAP ); and 3 strong SARs mapped to two interferon ω pseudogenes ( IFNWP ). One weak SAR mapped to the flanking region of one IFNA gene, whereas 6 weak SARs flanked four IFN pseudogenes ( P11, P12 P20, P23 ). The IFN SAR structure was comparable between the BV173 leukemia cell line and the U373 glioma cell line. Analysis of two glioma deletion breakpoint junctions, where breaks occur within and outside the IFN gene cluster, revealed an association with SARs. IFN SARs showed evidence for cooperativity among the SARs, while DNA sequence analysis revealed a series of clustered A-tracts within strong SARs. These data suggest that the IFN genes may be organized into a series of small (2–10 kb) DNA loop domains, with each loop containing a coding region flanked by SARs. In our model, the SAR enrichment and the clustering of A-tracts observed at the SARs within the IFN gene complex represent a higher level of chromatin organization, which may predispose this region to breakage.