p21 WAF-1 reorganizes the nucleus in tumor suppression (cancer geneticsychromatin architectureygenome organizationyp53)

Interphasic nuclear organization has a key function in genome biology. We demonstrate that p21 WAF-1 ,b y inf luencing gene expression and inducing chromosomal re- positioning in tumor suppression, plays a major role as a nuclear organizer. Transfection of U937 tumor cells with p21 WAF-1 resulted in expression of the HUMSIAH (human seven in absentia homologue), Rb, and Rbr-2 genes and strong sup- pression of the malignant phenotype. p21 WAF-1 drastically modified the compartmentalization of the nuclear genome. DNase I genome exposure and f luorescence in situ hybridiza- tion show, respectively, a displacement of the sensitive sites to the periphery of the nucleus and repositioning of chromo- somes 13, 16, 17, and 21. These findings, addressing nuclear architecture modulations, provide potentially significant per- spectives for the understanding of tumor suppression.