Intermingling of chromosome territories

Abstract

The importance of higher order nuclear structure and compartmentalization for the control of the cell life is now indisputable. The genome of higher eukaryotes is organized into definite chromosome territories, and the three‐dimensional organization of these territories may be intently related to genomic function, global regulation of gene expression, and even formation of exchange aberrations. In this review, we discuss our current understanding of the chromosome territories phenomenon and briefly describe how genes relocation in three‐dimensional arrangement of the genome may influence their functioning. We explain how the intermingling of the edges of chromosome territories allows the formation of rare long‐range interchromosomal interactions. Moreover, we illustrate recent discoveries describing the mechanisms of physical proximity‐based chromosome translocations and its clinical consequence for fusion genes formation and tumor development. Finally, we characterize the inner structure of the intermingled chromosomes briefly, and explain how chromosome intermingling affects gene expression regulation.

Profound alterations of the chromatin architecture at chromosome 11p15.5 in cells from Beckwith-Wiedemann and Silver-Russell syndromes patients

“…It is important to note that the inter-domain interactions between ICR2-region upstream of IGF2 and ICR2-CTCF Dw (H19) are monoallelic (3C-SNP data) and are cis-interactions (3D FISH data), and they move IGF2 close to ICR2 on one parental allele, and H19 into proximity to ICR2 on the other allele. These data suggest the involvement of a mechanism to coordinate genes with the same expression status, even those distant from each other, as previously described for other genes and regions 42 in this context, IGF2 and KCNQ1OT1 on the paternal allele and H19 and CDKN1C on the maternal allele.…”

Meiotic Chromosome Contacts as a Plausible Prelude for Robertsonian Translocations

“…Translocation probability rates could be higher if chromosomes were located close to each other in the nuclear space [24]. For intermingling chromosomes, DSBs in contact zones can lead to non-homologous linking and translocations [25,26]. In this context, the evolutionary integrative breakage model [27] stressed determining the genomic distribution of evolutionary breakpoints due to particular DNA sequence composition and the nucleome, combined with alteration of gene expression due to genome reshuffling.…”

The multi‐faceted regulation of nuclear tRNA gene transcription

“…Consistent with this, TFIIIC is now largely recognized as a factor that can shape genome architecture in both a tDNA-dependent and independent manner (100). Clustering of tDNA genes also appears to be mediated by RNAP III TFs through binding to condensin, a complex involved in the compaction of chromosomes (although spatial organization at the nucleus and clustering appear to occur through separate mechanisms) (98).…”

“…Regions of the genome that frequently physically interact with each other termed Topologically Associating Domains (TADs) have been described in the genomes of many organisms such as human , fruit fly , budding yeast , and plants . Transcription may be further influenced by an additional level of location complexity where these structures preferentially occupy areas around the nuclear center or periphery called chromosome territories . Hence, by compartmentalizing genes that have different transcriptional requirements, chromosomal architectures appear to be crucial orchestrators of expression and cell identities.…”