Differences in the Localization and Morphology of Chromosomes in the Human Nucleus

Abstract

Using fluorescence in situ hybridization we show striking differences in nuclear position, chromosome morphology, and interactions with nuclear substructure for human chromosomes 18 and 19. Human chromosome 19 is shown to adopt a more internal position in the nucleus than chromosome 18 and to be more extensively associated with the nuclear matrix. The more peripheral localization of chromosome 18 is established early in the cell cycle and is maintained thereafter. We show that the preferential localization of chromosomes 18 and 19 in the nucleus is reflected in the orientation of translocation chromosomes in the nucleus. Lastly, we show that the inhibition of transcription can have gross, but reversible, effects on chromosome architecture. Our data demonstrate that the distribution of genomic sequences between chromosomes has implications for nuclear structure and we discuss our findings in relation to a model of the human nucleus that is functionally compartmentalized.

Three-dimensional positioning of genes in mouse cell nuclei

“…Our results thus indicate a preference of gene loci for a particular subregion of the chromosome territory while the territory has itself a preferred radial nuclear position. This argues for a polar radial organization of chromosome territories, as has been suggested by others (Ferreira et al 1997;Croft et al 1999;Sadoni et al 1999;Saccone et al 2002;Scheuermann et al 2004;Küpper et al 2007).…”

“…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.…”

“…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. It now appears that in these flat, ellipsoid nuclei large chromo-somes are preferentially near the perimeter while small chromosomes are preferentially in a central cylinder and, in addition, gene-poor chromosome territories are in closer contact with the nuclear membrane than gene-rich ones (Bolzer et al 2005).…”

Parental genomes mix in mule and human cell nuclei

“…In vertebrates, a radial organization of chromosome territories was identified in human (Croft et al 1999), primate (Tanabe et al 2002), mouse (Mayer et al 2005), and chicken cell nuclei (Habermann et al 2001). Gene-rich as well as small chromosomes are preferentially at internal positions and gene-poor or large chromosomes at peripheral positions (for reviews, see Foster and Bridger 2005;Cremer et al 2006;Lanctôt et al 2007).…”

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

“…It is now well established that chromosomes are non-randomly positioned in the interphase nuclei of many eukaryotes such as humans, mice, chicken and plants (Croft, et al 1999;Habermann, et al 2001;Mayr, et al 2003;Mayer, et al 2005). 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).…”