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Abstract

The spatial arrangement of some genetic elements relative to chromosome territories and in parallel with the cell nucleus was investigated in human lymphocytes. The structure of the chromosome territories was studied in chromosomes containing regions (clusters) of highly expressed genes (HSA 9, 17) and those without such clusters (HSA 8, 13). In chromosomes containing highly expressed regions, the elements pertaining to these regions were found close to the centre of the nucleus on the inner sides of chromosome territories; those pertaining to regions with low expression were localized close to the nuclear membrane on the opposite sides of the territories. In chromosomes with generally low expression (HSA 8, 13), the elements investigated were found symmetrically distributed over the territories. Based on the investigations of the chromosome structure, the following conclusions are suggested: (1) Chromosome territories have a non-random internal 3D structure with defined average mutual positions between elements. For example, RARalpha, TP53 and Iso-q of HSA 17 are nearer to each other than they are to the HSA 17 centromere. (2) The structure of a chromosome territory reflects the number and chromosome location of clusters of highly expressed genes. (3) Chromosome territories behave to some extent as solid bodies: if the territory is found closer to the nuclear centre, the individual genetic elements of this chromosome are also found, on average, closer the centre of the nucleus. (4) The positions of centromeres are, on average, nearer to the fluorescence weight centre of the territory (FWCT) than to genes. (5) Active genes are not found near the centromeres of their own territory. A simple model of the structure of chromosome territory is proposed.

A Paradigm Revolution or Just Better Resolution—Will Newly Emerging Superresolution Techniques Identify Chromatin Architecture as a Key Factor in Radiation-Induced DNA Damage and Repair Regulation?

“…However, our hybrid model provides strong evidence that the chromatin architecture around a DSB may affect the probability of translocation between particular loci more strongly than the mutual distance between the loci in the nucleus if this distance is not large enough to be dominant [75]. As the functional architecture of chromatin determines both the nuclear gene topology [44][45][46]130,[194][195][196][197] and the vectors (extent and directions) of individual DSB movements relative to each other, it also defines the probability of mutual DSB interaction [48,75].…”

“…Moreover, chromatin is hierarchically organized at multiple scale levels, which leads to the formation of structurally and functionally distinct chromatin domains [44][45][46][47], with which radiation interacts in a specific way and creates DNA lesions with different requirements for repair (reviewed in [48][49][50][51][52]). The chemical properties of the broken DNA ends were the first local factor ( Figure 1D) recognized to dramatically affect the ability of repair enzymes to rejoin DSBs [53].…”

Radial chromatin positioning is shaped by local gene density, not by gene expression

“…The influence of transcriptional activity on gene positioning in the nucleus has been a controversial issue (for review, see Bartova and Kozubek 2006; Kosak and Groudine 2004; Lanctot et al 2007; Parada et al 2004). Lukasova et al 2002 and Scheuermann et al 2004 suggested an interior nuclear position of transcribed genes, compared to non-transcribed genes in a given cell type. As local gene density was not considered in these studies, these observations may rather reflect gene density than the transcriptional activity of a studied gene per se.…”

Radiation Induced Chromatin Conformation Changes Analysed by Fluorescent Localization Microscopy, Statistical Physics, and Graph Theory

“…One example of such domains is the distinction between decondensed, transcriptionally active euchromatin and tightly compacted heterochromatin generally to be assumed to be inactive [ 10 , 11 , 12 , 13 , 14 ]. Gene-rich regions tend to be located towards the nuclear interior whereas gene-poor regions are generally found towards the periphery [ 15 , 16 , 17 , 18 ]. Up-regulation of genes during tumour genesis or DNA radiation damage response as well as DNA double strand break repair mechanisms were shown to be associated with re-organisation of chromosome territories [ 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”