Transcriptional repression mediated by polycomb group proteins and other chromatin-associated repressors is selectively blocked by insulators

Polycomb group (PcG) proteins repress gene activity over a considerable dis tance, possibly by spreading along the chromatin fiber. Insulators or bound ary elements, genetic elements within the chromatin, may serve to terminate the repressing action of PcG proteins. We studied the ability of insulator s to block the action of chromatin-associated repressors such as PcG protei ns, HP1, and MeCP2. We found that the Drosophila special chromatin structur e insulator completely blocks transcriptional repression mediated by all of the repressors we tested. The Drosophila gypsy insulator was able to block the repression mediated by the PcG proteins Su(z)2 and RING1, as well as m HP1, but not the repression mediated by MeCP2 and the PcG protein HPC2. The 5'-located DNase I-hypersensitive site in the chicken beta-globin locus di splayed a limited ability to block repression, and a matrix or scaffold att achment region element was entirely unable to block repression mediated by any repressor tested. Our results indicate that insulators can block repres sion mediated by PcG proteins and other chromatin-associated repressors, bu t with a high level of selectivity. This high degree of specificity may pro vide a useful assay to define and characterize distinct classes of insulato rs.