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2017 ; 31
(2
): 141-153
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Comprehensive characterization of neutrophil genome topology
#MMPMID28167501
Zhu Y
; Gong K
; Denholtz M
; Chandra V
; Kamps MP
; Alber F
; Murre C
Genes Dev
2017[Jan]; 31
(2
): 141-153
PMID28167501
show ga
Neutrophils are responsible for the first line of defense against invading
pathogens. Their nuclei are uniquely structured as multiple lobes that establish
a highly constrained nuclear environment. Here we found that neutrophil
differentiation was not associated with large-scale changes in the number and
sizes of topologically associating domains (TADs). However, neutrophil genomes
were enriched for long-range genomic interactions that spanned multiple TADs.
Population-based simulation of spherical and toroid genomes revealed declining
radii of gyration for neutrophil chromosomes. We found that neutrophil genomes
were highly enriched for heterochromatic genomic interactions across vast genomic
distances, a process named supercontraction. Supercontraction involved genomic
regions located in the heterochromatic compartment in both progenitors and
neutrophils or genomic regions that switched from the euchromatic to the
heterochromatic compartment during neutrophil differentiation. Supercontraction
was accompanied by the repositioning of centromeres, pericentromeres, and long
interspersed nuclear elements (LINEs) to the neutrophil nuclear lamina. We found
that Lamin B receptor expression was required to attach centromeric and
pericentromeric repeats but not LINE-1 elements to the lamina. Differentiating
neutrophils also repositioned ribosomal DNA and mininucleoli to the lamina-a
process that was closely associated with sharply reduced ribosomal RNA
expression. We propose that large-scale chromatin reorganization involving
supercontraction and recruitment of heterochromatin and nucleoli to the nuclear
lamina facilitates the folding of the neutrophil genome into a confined geometry
imposed by a multilobed nuclear architecture.
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