Evidence for the organization of chromatin in megabase pair-sized loops arranged along a random walk path in the human G0/G1 interphase nucleus.

Yokota, Hiroki; Engh, Ger van den; Hearst, John E.; Sachs, Rainer K.; Trask, Barbara J.

doi:10.1083/jcb.130.6.1239

Cited by 272 publications

(224 citation statements)

References 42 publications

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“…The experimental observations (9,34,35) Measurements of K from previous models produce a constant value of K. The randomly folded polymer (SAW) model produces K ¼ 1.5 (22). Previous polymer models that consider the effects of both specified chromatin loops at fixed lengths of 120 kb and 3 Mb (12,36), and the possibility of chromatin loops of all sizes (37), also produce constant K values.…”

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

confidence: 99%

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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%

“…In principle, K carries information about genomic locus-to-locus and cell-to-cell variations. Interestingly, K has been measured experimentally by FISH (9,34,35) and found to vary between 1.5 and 4.4, depending on the locus and cell type studied (Fig. 4A).…”

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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“…19,20,[22][23][24]. In one effort, a three-color barcoding approach has been used to simultaneously label multiple chromatin loci to trace the conformation of a chromosome arm in Drosophila blastoderm embryos (24).…”

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confidence: 99%

Spatial Organization of Chromatin Domains and Compartments in Single Chromosomes

Wang

Beliveau

et al. 2017

Biophysical Journal

203

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The spatial organization of chromatin critically impacts genome function. Recent chromosomeconformation-capture studies have revealed topologically-associating domains (TADs) as a conserved feature of chromatin organization, but how TADs are spatially organized in individual chromosomes remains unknown. Here we developed an imaging method for mapping the spatial positions of numerous genomic regions along individual chromosomes and traced the positions of TADs in human interphase autosomes and X chromosomes. We observed that chromosome folding deviates from the ideal fractal-globule model at large length scales and that TADs are largely organized into two compartments spatially arranged in a polarized fashion in individual chromosomes. Active and inactive X chromosomes adopt different folding and compartmentalization configurations. These results suggest that the spatial organization of chromatin domains can change in response to regulation.The spatial organization of chromatin, such as chromatin domains, chromatin loops, associations of chromatin with nuclear structures, and chromosome territories, plays an important role in essential genome functions (1-6). However, many gaps remain in our understanding of the three-dimensional (3D) folding of individual chromosomes in the nucleus. Recently, chromosome-conformation-capture methods such as Hi-C (4, 7) have revealed a wealth of structural insights for interphase chromosomes. For example, chromatin is organized into topologically-associating domains (TADs) or contact domains that are hundreds of kilobases (kb) in size (8-11). These domains tend to spatially segregate from each other (9, 12, 13) and, in Drosophila, correspond to the banding patterns of polytene chromosomes (14, 15). At length scales from several hundred kilobases to several megabases, the power-law scaling of Hi-C contact frequency is consistent with a fractalglobule polymer model (7, 16), whereas, within TADs, Hi-C contact maps are better

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“…Therefore, the number of attractive sites suggested by the evaluation of the diameter, namely about 11 per 1 Mbp domain, is consistent with the number proposed by the exponent. The exponent of 0.32±0.02 was obtained by Münkel [15] based on the experiments by Yokota et al [38] for genomic distances of several Mbps. The parameter range yielded by our simulation results is therefore in good agreement with experiment.…”

Section: Simulation Resultsmentioning

confidence: 99%

Dynamic Simulation of Active/Inactive Chromatin Domains

2005

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Abstract. In the present study a model for the compactification of the 30 nm chromatin fibre into higher order structures is suggested. The idea is that basically every condensing agent (HMG/SAR, HP1, cohesin, condensin, DNA-DNA interaction . . . ) can be modeled as an effective attractive potential of specific chain segments. This way the formation of individual 1 Mbp sized rosettes from a linear chain could be observed. We analyse how the size of these rosettes depends on the number of attractive segments and on the segment length. It turns out that 8-20 attractive segments per 1 Mbp domain produces rosettes of 300-800 nm in diameter. Furthermore, our results show that the size of the rosettes is relatively insensitive to the segment length.

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Evidence for the organization of chromatin in megabase pair-sized loops arranged along a random walk path in the human G0/G1 interphase nucleus.

Cited by 272 publications

References 42 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

Spatial Organization of Chromatin Domains and Compartments in Single Chromosomes

Dynamic Simulation of Active/Inactive Chromatin Domains

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