Intermingling of Chromosome Territories in Interphase Suggests Role in Translocations and Transcription-Dependent Associations

By M. Branco, A. Pombo. PLoS Biology, 2006

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After mitosis, mammalian chromosomes partially decondense to occupy distinct territories in the cell nucleus. Current models propose that territories are separated by an interchromatin domain, rich in soluble nuclear machinery, where only rare interchromosomal interactions can occur via extended chromatin loops. In contrast, recent evidence for chromatin mobility and high frequency of chromosome translocations are consistent with significant levels of chromosome intermingling, with important consequences for genome function and stability. Here we use a novel high-resolution in situ hybridization procedure that preserves chromatin nanostructure to show that chromosome territories intermingle significantly in the nucleus of human cells. The degree of intermingling between specific chromosome pairs in human lymphocytes correlates with the frequency of chromosome translocations in the same cell type, implying that double-strand breaks formed within areas of intermingling are more likely to participate in interchromosomal rearrangements. The presence of transcription factories in regions of intermingling and the effect of transcription impairment on the interactions between chromosomes shows that transcription-dependent interchromosomal associations shape chromosome organization in mammalian cells. These findings suggest that local chromatin conformation and gene transcription influence the extent with which chromosomes interact and affect their overall properties, with direct consequences for cell-type specific genome stability.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/55079af5c640b3bef1fac32f30702326db7c0384

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Citations in the corpus

Aging Hematopoietic Stem Cells Decline in Function and Exhibit Epigenetic Dysregulation (2007, background): “Moreover, IgK alleles have been shown to be differentially located within the nucleus depending on their state of activation [47], which could result in their juxtaposition to oncogenes, increasing the likelihood of translocation [48].”
Polymers with spatial or topological constraints: Theoretical and computational results (2011, background): “Indeed, this mechanism is believed to be an important ingredient in the spatial organization and segregation of highly confined DNA molecules such as bacterial chromosomes [235] and eukaryotic chromosomes during interphase [236, 85] (see the discussion in Section 16.”
Higher-order inter-chromosomal hubs shape 3D genome organization in the nucleus (2018, background): “, 2003) and may explain previous observations that actively transcribed gene-dense regions can “loop out” from the core chromosome territory (Branco and Pombo, 2006; Mahy et al., 2002).”
Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data (2013, background): “Second, where chromosome territories touch, they can form areas in which intermingling occurs, providing opportunities for potentially functional interactions between loci located on different chromosomes 9 .”
Beyond the sequence: cellular organization of genome function. (2007, positive): “Even though it is clear that neither all highly transcribed regions nor all transcribed gene clusters form giant loops, a recent highresolution in situ hybridization method revealed a higher degree of intermingling between neighboring chromosomes than previously was assumed, which suggests that larg”
Complex multi-enhancer contacts captured by Genome Architecture Mapping (GAM) (2017, neutral): “We applied GAM to mouse embryonic stem cells (mESCs) where abundant data is available relating to chromatin contacts and chromatin occupancy at enhancers and promoters5,26,32– 35. mESCs were fixed in optimal conditions, and cryosectioned at a thickness of ~0.22 μm 30,31,36,37.”
Dynamic genome architecture in the nuclear space: regulation of gene expression in three dimensions (2007, methodology): “Using three-dimensional fluorescence in situ hybridization (FISH) on thin cryosections, Branco and Pombo reported extensive intermingling of chromati”
Chromosome territories. (2010, methodology): “(C) According to the interchromatin network (ICN) model (Branco and Pombo 2006), intermingling chromatin fibers/loops from the same CT, as well as from neighboring CTs, can make contact in cis and trans.”