Gene density and chromosome territory shape

Abstract

Despite decades of study of chromosome territories (CT) in the interphase nucleus of mammalian cells, our understanding of the global shape and 3-D organization of the individual CT remains very limited. Past microscopic analysis of CT suggested that, while many of the CT appear to be very regular ellipsoid-like shapes, there were also those with more irregular shapes. We have undertaken a comprehensive analysis to determine the degree of shape regularity of different CT. To be representative of the whole human genome, 12 different CT (~41% of the genome) were selected that ranged from the largest (CT 1) to the smallest (CT 21) in size and from the highest (CT 19) to lowest (CT Y) in gene density. Using both visual inspection and algorithms that measure the degree of shape ellipticity and regularity, we demonstrate a strong inverse correlation between the degree of regular CT shape and gene density for those CT that are most gene rich (19, 17, 11) and gene poor (18, 13, Y). CT more intermediate in gene density, showed a strong negative correlation with shape regularity but not with ellipticity. An even more striking correlation between gene density and CT shape was determined for the nucleolar associated NOR-CT. Correspondingly striking differences in shape between the X active and inactive CT implied that, aside from gene density, the overall global level of gene transcription on individual CT is also an important determinant of chromosome territory shape.

Chromosome Conformation of Human Fibroblasts Grown in 3-Dimensional Spheroids

“…1A). We also applied ICE 25 to our data for normalization, which produced very similar result (Fig. 1B).…”

“…Subsequent analyses were performed on the RPM-normalized Hi-C matrices. We used this RPM normalization since further, more sophisticated normalization 25 produced similar results (see Fig. 1B).…”

Chromosome territories and the global regulation of the genome

“…CT display a wide range of 3‐D shapes from regular ellipsoid‐like to highly irregular . Properties that could influence the global organization of individual CT include heterochromatin/euchromatin levels and arrangements, gene density, RIDGES/ANTI‐RIDGES, and overall levels of gene activity . A higher degree of irregularity in CT shape is found with increasing gene density .…”

Chromosomes at Work: Organization of Chromosome Territories in the Interphase Nucleus

“…Outside of mitosis, overall CT morphologies were demonstrated to be maintained for up to 4 h in the cell cycle [Edelmann et al, ; Muller et al, ]; however, alterations were detected in internal CT organization [Muller et al, ]. CT morphology was found to be altered, however, in studies that examined CTs in G1 compared to S‐phase nuclei [Sehgal et al, ]. Along with this altered CT morphology, cell‐type specific alterations in the interchromosomal organization of specific CT were demonstrated [Fritz et al, ].…”