The Radial Positioning of Chromatin Is Not Inherited through Mitosis but Is Established De Novo in Early G1

Abstract

The organization of chromatin in the nucleus is nonrandom. Different genomic regions tend to reside in preferred nuclear locations, relative to radial position and nuclear compartments. Several lines of evidence support a role for chromatin localization in the regulation of gene expression. Therefore, a key problem is how the organization of chromatin is established and maintained in dividing cell populations. There is controversy about the extent to which chromatin organization is inherited from mother to daughter nucleus. We have used time-lapse microscopy to track specific human loci after exit from mitosis. In comparison to later stages of interphase, we detect increased chromatin mobility during the first 2 hr of G1, and during this period association of loci with nuclear compartments is both gained and lost. Although chromatin in daughter nuclei has a rough symmetry in its spatial distribution, we show, for the first time, that the association of loci with nuclear compartments displays significant asymmetry between daughter nuclei and therefore cannot be inherited from the mother nucleus. We conclude that the organization of chromatin in the nucleus is not passed down precisely from one cell to its descendents but is more plastic and becomes refined during early G1.

Chromosome Conformation of Human Fibroblasts Grown in 3-Dimensional Spheroids

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. However, intra-contacts were significantly reduced on HSA 16, 17, 19, 20q, 22, and 1pter (supplementary Figs.…”

“…13 However, other investigations find loss of order during transmission, as well as variations in CT neighborhood from one cell cycle to the next. 14,15 As a whole, these studies show that an understanding of the 3 dimensional genome requires approaches that address its dynamical nature.…”

The genome and the nucleus: a marriage made by evolution

“…On the wheel-shaped rosette of the metaphase plate, chromosomes are attached via their kinetochores, this would result in the smaller chromosomes' arms being more centrally located on the rosette and the larger chromosomes' arms being further away in distance from the centre of the rosette (Sun et al 2000). Theoretically, this pattern would be preserved in G1 (Sun et al 2000), and it has been shown by others that chromosome position can change dramatically in G1 (Bridger et al 2000;Walter et al 2003;Thomson et al 2004). In the Sun study, no telomeric probes were used for the p arms of chromosomes and because it is possible that the p and q arms may occupy different positions in regard to each other (Dietzel et al 1998a,b), especially in the larger sized chromosomes, the positioning of telomeres does not necessarily provide accurate information about the whole positioning of a chromosome territory, which is usually elicited when delineating a whole chromosome territory.…”

Chromatin at the nuclear periphery and the regulation of genome functions

“…Therefore, the nuclear lamina and the nucleolus might provide two alternative locations where the same repressive genomic domains can partition. Indeed, analysis of mother and daughter cells through mitosis reveals that loci originally at the nuclear periphery in a mother cell can relocate either to the nuclear periphery or to the periphery of the nucleolus in the daughter cells (Thomson et al 2004;Kind et al 2013). …”