Chromatin domains and the interchromatin compartment form structurally defined and functionally interacting nuclear networks

Albiez, Heiner; Cremer, Marion; Tiberi, Cinzia; Vecchio, Lorella; Schermelleh, Lothar; Dittrich, Sandra; Küpper, Katrin; Joffe, Boris; Thormeyer, Tobias; Hase, Johann von; Yang, Siwei; Rohr, Karl; Leonhardt, Heinrich; Solovei, Irina; Cremer, Christoph; Fakan, Stanislav; Cremer, Thomas

doi:10.1007/s10577-006-1086-x

Cited by 250 publications

(263 citation statements)

References 86 publications

(104 reference statements)

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“…S1A, S2, S4, and S5). Nevertheless, the FG model may help explain specific transitional states for some genomic regions, as, for instance, rapid chromatin decondensation and chromatin looping out of chromosome territories during gene activation (27)(28)(29)(30)(31).…”

Section: Comparison Of the Sbs And Other Models Against Experimental mentioning

confidence: 99%

Complexity of chromatin folding is captured by the strings and binders switch model

Barbieri

Chotalia

Fraser

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

552

688

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Chromatin has a complex spatial organization in the cell nucleus that serves vital functional purposes. A variety of chromatin folding conformations has been detected by single-cell imaging and chromosome conformation capture-based approaches. However, a unified quantitative framework describing spatial chromatin organization is still lacking. Here, we explore the "strings and binders switch" model to explain the origin and variety of chromatin behaviors that coexist and dynamically change within living cells. This simple polymer model recapitulates the scaling properties of chromatin folding reported experimentally in different cellular systems, the fractal state of chromatin, the processes of domain formation, and looping out. Additionally, the strings and binders switch model reproduces the recently proposed "fractal-globule" model, but only as one of many possible transient conformations.genome organization | genome architecture | long-range chromatin interactions | fluorescence in situ hybridization | Monte Carlo simulations U nderstanding the interplay between genome architecture and gene regulation is one of the most challenging problems in biology. During mitosis, chromosomes are found in a condensed state, but decondense during interphase, when highly coordinated cellular processes such as transcription, DNA repair, and replication take place, creating cell-type-specific chromatin folding (1-3).Chromosome organization occurs at different scales of genomic length to yield variable degrees of compaction (4). Linear nucleosome arrays fold into higher-order structures, first through local chromatin interactions, such as between promoters and enhancers, and then eventually giving rise to discrete chromosome territories (1).Spatial genome organization is guided by intra-and interchromosomal interactions mediated by nuclear components that include transcription factors, transcription and replication factories, Polycomb bodies, and contacts with the lamina (5-8). However, how binding of diffusible factors to specific genomic regions drives chromatin folding remains poorly understood.Imaging of single loci by FISH and genome-wide mapping of chromatin interactions by chromosome conformation capture (3C) approaches revealed a variety of chromatin architectures across genomic regions and cell types, and upon environmental cues (9-14) (Fig. S1A). In FISH experiments, chromatin folding is often measured by the mean-square spatial distance, R 2 ðsÞ, between two genomic regions as a function of their linear genomic distance, s (Fig. S1B), which usually exhibits scaling properties R 2 ðsÞ ∼ s 2v . Although the behavior of R 2 ðsÞ appears to depend on the genomic regions and cell types assessed (Fig. S1A), in general, at large genomic distances, R 2 ðsÞ reaches a plateau (i.e., v ¼ 0) that reflects the folding of chromosomes into territories (15).A global analysis of genome-wide 3C (Hi-C) ligation products in human cells averaged across all chromosomes has been used to estimate the "contact probability," P c ðsÞ (13). Th...

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Section: Comparison Of the Sbs And Other Models Against Experimental mentioning

confidence: 99%

Complexity of chromatin folding is captured by the strings and binders switch model

Barbieri

Chotalia

Fraser

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

552

688

View full text Add to dashboard Cite

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“…According to the chromosome territory-interchromatin compartment model, chromosome territories are composed of a complex configuration of compact chromatin domains with a network of spaces between the compact chromatin and between adjacent chromosomes [23]. In this model, active genes are positioned at the periphery of the compact chromatin subdomains and between adjacent chromosomes where they are exposed to regulatory molecules and transcription factories.…”

Section: Nuclear Organization In Normal and Cancer Cellsmentioning

confidence: 99%

The role of nuclear organization in cancer

Lever¹,

Sheer²

2009

The Journal of Pathology

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The functional significance of changes in nuclear structure and organization in transformed cells remains one of the most enigmatic questions in cancer biology. In this review, we discuss relationships between nuclear organization and transcription in terms of the threedimensional arrangement of genes in the interphase cancer nucleus and the regulatory functions of nuclear matrix proteins. We also analyse the role of nuclear topology in the generation of gene fusions. We speculate that this type of multi-layered analysis will one day provide a framework for a more comprehensive understanding of the genetic origins of cancer and the identification of new therapeutic targets.

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“…Absolute 3D distance measurements from signal voxels to the nearest surface of the nucleus was performed with the software eADS, written by Tobias Thormeyer, Munich (Albiez et al 2006), after an algorithm by Johann von Hase, Heidelberg. Briefly, at the determined threshold, a surface around the reference object (nucleus) is computed.…”

Section: Image Processing and Analysismentioning

confidence: 99%

Parental genomes mix in mule and human cell nuclei

et al. 2009

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Whether chromosome sets inherited from father and mother occupy separate spaces in the cell nucleus is a question first asked over 110 years ago. Recently, the nuclear organization of the genome has come increasingly into focus as an important level of epigenetic regulation. In this context, it is indispensable to know whether or not parental genomes are spatially separated. Genome separation had been demonstrated for plant hybrids and for the early mammalian embryo. Conclusive studies for somatic mammalian cell nuclei are lacking because homologous chromosomes from the two parents cannot be distinguished within a species. We circumvented this problem by investigating the three-dimensional distribution of chromosomes in mule lymphocytes and fibroblasts. Genomic DNA of horse and donkey was used as probes in fluorescence in situ hybridization under conditions where only tandem repetitive sequences were detected. We thus could determine the distribution of maternal and paternal chromosome sets in structurally preserved interphase nuclei for the first time. In addition, we investigated the distribution of several pairs of chromosomes in human bilobed granulocytes. Qualitative and quantitative image evaluation did not reveal any evidence for the separation of parental genomes. On the contrary, we observed mixing of maternal and paternal chromosome sets.

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Chromatin domains and the interchromatin compartment form structurally defined and functionally interacting nuclear networks

Cited by 250 publications

References 86 publications

Complexity of chromatin folding is captured by the strings and binders switch model

Complexity of chromatin folding is captured by the strings and binders switch model

The role of nuclear organization in cancer

Parental genomes mix in mule and human cell nuclei

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