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Blood, Vol. 95 No. 5 (March 1), 2000:
pp. 1608-1615
Spatial associations of centromeres in the nuclei of hematopoietic
cells: evidence for cell-type-specific organizational
patterns
Isabel Alcobia,
Rui Dilão, and
Leonor Parreira
From the Institute of Histology and Embryology, Lisbon Medical
School, and the Nonlinear Dynamics Group, IST Department of Physics,
Lisbon, Portugal.
It is believed that the 3-dimensional organization of centromeric
heterochromatin in interphase may be of functional relevance as an
epigenetic mechanism for the regulation of gene expression. Accordingly, a likely possibility 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 model, the chromocenters observed in quiescent normal human hematopoietic cells
and primary fibroblasts. To do this, we analyzed the spatial relationships among different human centromeres in 3-D preserved cells
using nonisotopic in situ hybridization and confocal microscopy. We
showed quantitatively that chromocenters in all cell types do indeed
represent nonrandom spatial associations of certain centromeres.
Furthermore, the observed patterns of centromere association indicate
that the chromocenters in these cell types are made of different
combinations of specific centromeres, that hematopoietic cells are
strikingly different from fibroblasts as to the composition of their
chromocenters and that centromeres in peripheral blood cells appear to
aggregate into distinct "myeloid" (present in monocytes and
granulocytes) and "lymphoid" (present in lymphocytes) spatial
patterns. These findings support the idea that the chromocenters formed
in the nucleus of quiescent hematopoietic cells might represent
heterochromatic 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 during hematopoietic differentiation.

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