We show that several transcriptionally inactive genes localize to centromer
ic heterochromatin in the nucleus of cycling but not quiescent (noncycling)
primary B lymphocytes. In quiescent cells, centromeric repositioning of in
active loci was induced after mitogenic stimulation. A dynamic repositionin
g of selected genes was also observed in developing T cells. Rag and TdT lo
ci were shown to relocate to centromeric domains following heritable gene s
ilencing in primary CD4(+)8(+) thymocytes, but not in a phenotypically simi
lar cell line in which silencing occurred but was not heritable. Collective
ly, these data indicate that the spatial organization of genes in cycling a
nd noncycling lymphocytes is different and that locus repositioning may be
a feature of heritable gene silencing.