Evolutionarily conserved, cell type and species-specific higher order chromatin arrangements in interphase nuclei of primates

Abstract

Several studies demonstrated a gene-density-correlated radial organization of chromosome territories (CTs) in spherically shaped nuclei of human lymphocytes or lymphoblastoid cells, while CT arrangements in flat-ellipsoidal nuclei of human fibroblasts are affected by both gene density and chromosome size. In the present study, we performed fluorescence in situ hybridization (FISH) experiments to three-dimensionally preserved nuclei (3D-FISH) from human and nonhuman primate cultured lymphoblastoid cells and fibroblasts. We investigated apes, Old, and New World monkeys showing either evolutionarily conserved karyotypes, multiple translocations, fusions, or serial fissions. Our goal was to test whether cell type specific differences of higher order chromatin arrangements are evolutionarily conserved in different primate lineages. Whole genome painting experiments and further detailed analyses of individual chromosomes indicate a gene-density-correlated higher order organization of chromatin in lymphoblastoid cell nuclei of all studied primate species, despite evolutionary chromosome reshuffling. In contrast, in primate fibroblast nuclei evolutionary translocations, fissions and fusions resulted in positional shifts of orthologous chromosome segments, thus arguing against a functional role of chromosome size-dependent spatial chromatin arrangements and for geometrical constraints in flat-ellipsoidal fibroblast nuclei. Notably, in both cell types, regions of rearranged chromosomes with distinct differences in gene density showed polarized arrangements with the more gene-dense segment oriented towards the nuclear interior. Our results indicate that nonrandom breakage and rejoining of preferentially gene-dense chromosomes or chromosome segments may have occurred during evolution.

The radial arrangement of the human chromosome 7 in the lymphocyte cell nucleus is associated with chromosomal band gene density

“…This type of nuclear chromosome distribution was first shown for the human chromosomes 18 and 19, which are located in different radial positions, namely at the periphery and in the interior of the nucleus, respectively (Croft et al 1999). Indeed, in spite of their similar size, these two chromosomes are endowed with very different gene densities, the former being very gene-poor, and the latter very gene-rich (Saccone et al 1992; where the nuclear location of the syntenic chromosomes shows a similar distribution in the spherical nuclei of lymphoblastoid cells, indicating that there is a highly conserved evolutionary trend in this specific cell type (Tanabe et al 2002b;Neusser et al 2007). …”

Three-dimensional positioning of genes in mouse cell nuclei

“…During interphase, chromosomes occupy a restricted space in the cell nucleus, the chromosome territory Meaburn and Misteli 2007). A nonrandom distribution of chromosome territories was described in nuclei of human origin (Croft et al 1999;Cremer et al 2001;Bolzer et al 2005;Wiblin et al 2005) from other primates (Tanabe et al 2002;Neusser et al 2007), mice (Parada et al 2004;Mayer et al 2005), and chicken (Habermann et al 2001;Stadler et al 2004). While in spherical lymphocyte nuclei of humans and other primates, a sorting of gene-dense chromosome territories towards the center and of gene-poor ones towards the nuclear periphery was the dominant pattern; findings in fibroblast nuclei (Croft et al 1999;Boyle et al 2001;Cremer et al 2001) were more difficult to interpret.…”

Position of human chromosomes is conserved in mouse nuclei indicating a species-independent mechanism for maintaining genome organization

“…Various lines of evidence from studies on nuclei from humans and other primate species strongly suggest that the nuclear center is a particularly favorable milieu for placing gene dense chromosomes, while the nuclear periphery with its associated heterochromatin favors gene poor chromosomes (Craig, et al 1997;Bolzer, et al 2005;Neusser, et al 2007). …”

“…In most cell types across species, gene dense chromosomes are positioned predominantly towards the nuclear center while chromosomes with lower gene densities are positioned towards the nuclear periphery (Croft, et al 1999;Habermann, et al 2001;Mayer, et al 2005;Lanctot, et al 2007). Despite extensive genomic rearrangement throughout evolution, such a non-random arrangement has been conserved in higher primates over a span of 30 million years, suggesting a strong functional significance of this higher order nuclear architecture (Tanabe, et al 2002;Tanabe, et al 2005;Mora, et al 2006;Neusser, et al 2007). Despite the apparent importance of this biological phenomenon, little is known about the underlying mechanism.…”

“…In the chicken, for instance, early replicating gene dense microchromosomes are more centrally positioned than late replicating gene poor macrochromosomes (Habermann, et al 2001). The homogeneously sized chromosomes of the primate species Wolf's Guenon are distinctly positioned with gene dense chromosomes predominantly in the nuclear center (Neusser, et al 2007). Both 2D and 3D-FISH analyses of cells containing translocation chromosomes show that the more gene dense partner is predominantly more centrally positioned than the gene poor partner (Croft et al 1999, Cremer et al 2003.…”