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2015 ; 8
(ä): 47
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Remodeling of nuclear landscapes during human myelopoietic cell differentiation
maintains co-aligned active and inactive nuclear compartments
#MMPMID26579212
Hübner B
; Lomiento M
; Mammoli F
; Illner D
; Markaki Y
; Ferrari S
; Cremer M
; Cremer T
Epigenetics Chromatin
2015[]; 8
(ä): 47
PMID26579212
show ga
BACKGROUND: Previous studies of higher order chromatin organization in nuclei of
mammalian species revealed both structural consistency and species-specific
differences between cell lines and during early embryonic development. Here, we
extended our studies to nuclear landscapes in the human myelopoietic lineage
representing a somatic cell differentiation system. Our longterm goal is a search
for structural features of nuclei, which are restricted to certain cell
types/species, as compared to features, which are evolutionary highly conserved,
arguing for their basic functional roles in nuclear organization. RESULTS: Common
human hematopoietic progenitors, myeloid precursor cells, differentiated
monocytes and granulocytes analyzed by super-resolution fluorescence microscopy
and electron microscopy revealed profound differences with respect to global
chromatin arrangements, the nuclear space occupied by the interchromatin
compartment and the distribution of nuclear pores. In contrast, we noted a
consistent organization in all cell types with regard to two co-aligned networks,
an active (ANC) and an inactive (INC) nuclear compartment delineated by
functionally relevant hallmarks. The ANC is enriched in active RNA polymerase II,
splicing speckles and histone signatures for transcriptionally competent
chromatin (H3K4me3), whereas the INC carries marks for repressed chromatin
(H3K9me3). CONCLUSIONS: Our findings substantiate the conservation of the
recently published ANC-INC network model of mammalian nuclear organization during
human myelopoiesis irrespective of profound changes of the global nuclear
architecture observed during this differentiation process. According to this
model, two spatially co-aligned and functionally interacting active and inactive
nuclear compartments (ANC and INC) pervade the nuclear space.