ISWI with my little eye

Condensed chromatin presents a barrier to access for the DNA replication machinery. In an Advanced Online Publication in Nature Genetics, Nadine Collins and colleagues describe the role of chromatin-remodeling complexes during the replication of pericentric heterochromatin regions (Nature Genetics, doi:10.1038/ng1046, 18 November 2002). Immunostaining experiments revealed that the ISWI-ACF1 (ATP-utilizing chromatin assembly and remodeling factor 1) complex is co-localized with pericentric heterochromatin in mouse fibroblast cells during replication. Knocking out ACF1 function, by RNA interference, impaired the DNA replication of pericentric heterochromatin during late S phase and blocked cell cycle progression. This was reversed by decondensing chromatin by other means (using 5-aza-2-deoxycytidine - a DNA methylation inhibitor). Thus remodeling by the ACF1-ISWI complexes appears necessary to allow movement of the replication fork through condensed heterochromatin regions.