Spacial associations of centromeres in the nuclei of hematopoietic cells: evidence for cell-type-specific organizational patterns

It is believed that the 3-dimensional organization of centromeric heterochr omatin in interphase may be of functional relevance as an epigenetic mechan ism for the regulation of gene expression. Accordingly, a likely possibilit y is that the centromeres that spatially associate into the heterochromatic structures (chromocenters) observed in the G1 phase of the cell cycle will differ in different cells. We sought to address this issue using, as a mod el, the chromocenters observed in quiescent normal human hematopoietic cell s and primary fibroblasts. To do this, we analyzed the spatial relationship s 3-D preserved cells using nonisotopic in situ hybridization and confocal microscopy. We showed quantitatively that chromocenters in ail cell types d o indeed represent nonrandom spatial associations of certain centromeres. F urthermore, the observed patterns of centromere association indicate that t he chromocenters in these cell types are made of different combinations of specific centromeres, that hematopoietic cells are strikingly different fro m fibroblasts as to the composition of their chromocenters and that centrom eres in peripheral blood cells appear to aggregate into distinct "myeloid" (present in monocytes and granulocytes) and "lymphoid" (present in lymphocy tes) spatial patterns. These findings support the idea that the chromocente rs formed in the nucleus of quiescent hematopoietic cells might represent h eterochromatic nuclear compartments involved in the regulation of cell-type -specific gene expression, further suggesting that the spatial arrangement of centromeric heterochromatin in interphase is ontogenically determined du ring hematopoietic differentiation. (C) 2000 by The American Society of Hem atology.