Nuclear topography of beta-like globin gene cluster in IL-3-stimulated human leukemic K-562 cells.

The beta-like globin genes, Ggamma, Agamma, delta and beta, forming specific clusters on chromosome 11, are transcriptionally regulated by the locus control region (LCR). The members of beta-like globin gene cluster (11p15.4) are variously switched during ontogenetic dependent erythropoiesis; however, changes of globin gene expression can be also observed during erythroid differentiation of bone marrow cells. In our experiments, interleukin-3 (IL-3)-stimulated human leukemic K-562 cells were used as a model system in which nuclear organization and expression of the beta-like globin gene cluster was investigated. In addition, the influence of IL-3 on the arrangement of chromosome 11 territory was analyzed. We observed that the beta-globin gene is not expressed in progenitor (nondifferentiated) K-562 cells, but is, however, activated after IL-3 stimulation of the K-562 population. A similar nuclear location of beta-like globin gene clusters was found in both control and IL-3-treated cells, which indicates that changes in cluster gene expression are accompanied by conserved nuclear topography of the gene cluster studied. On the other hand, the studied type of cell differentiation was characterized by relocation of chromosome 11 and its centromeric regions closer to the nuclear periphery, which seems to be a general feature of many pathways of cellular maturation. The beta-like globin gene cluster was observed on chromatin loops extended away from compact chromosome 11 territories that were more condensed in regions closer to the nuclear membrane. The relocation of chromosome 11 territories towards the nuclear periphery and simultaneous appearance of chromatin loops may explain the conserved nuclear positioning of the gene cluster studied.