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

Miguel R. Branco ¹, Ana Pombo ^1, *

¹ MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom

* To whom correspondence should be addressed. E-mail: ana.pombo@csc.mrc.ac.uk

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.

Copyright: © 2006 Branco and Pombo. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abbreviations: 3D, three-dimensional; CT, chromosome territory; DSB, double-strand break; EM, electron microscopy; FISH, fluorescence in situ hybridization; ICD, interchromatin domain; IFN-g, interferon-gamma; LM, light microscopy; Pol, RNA polymerase

Additional References:

1. Frenster JH, and Hovsepian JA, "Ultrastructure of Euchromatin Contact Points between the Closed Loops of Adjacent Interphase Chromosomes".

2. Xu N, Tsai C-L, Lee JT,
"Transient Homologous Chromosome Pairing Marks the Onset of X Inactivation".

3. Bacher CP, Guggiari M, Brors B, Augui S, Clerc P, Avner P, Eils R, and Heard E,
"Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation".

4. Frenster JH, and Rogoway WM, "Immunotherapy of Human Neoplasms with Autologous Lymphocytes Activated In-Vitro".
 

Links to RNA and Biological Causality:

Links to Euchromatin Activator RNA Reviews:
Links to Euchromatin Activator RNA Research:
Links to Ultrastructural Probes of DNase I-Sensitive Sites:
Links to RNA as a Therapeutic Agent:
Links to Hodgkin Lymphoma Immuno-Pathology:
Links to Activated T-Lymphocyte Immunotherapy:
Links to Medical Systems Biology:
Links to Selective Gene Transcription:
Links to RNA-Induced Epigenetics:
Links to RNA-Induced Embryogenesis:
Links to RNA and Biological Causality:
Links to Reprogramming and Neoplasia:

"Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA".

For Further Information and Feedback:
Phone:  +1 650 367 6483
E-mail: frenster@euchromatin.net