A random-walk/giant-loop model for interphase chromosomes.

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

doi:10.1073/pnas.92.7.2710

Cited by 283 publications

(258 citation statements)

References 11 publications

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“…On the basis of these findings, we propose a random walk/giant loop model for interphase chromosomes. The mathematical details of this model, based on the data presented below, are being presented elsewhere (Sachs et al, 1995).…”

mentioning

confidence: 99%

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

Engh

Hearst

et al. 1995

The Journal of Cell Biology

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272

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Abstract. We determined the folding of chromosomes in interphase nuclei by measuring the distance between points on the same chromosome. Over 25,000 measurements were made in G0/G1 nuclei between DNA sequences separated by 0.15-190 megabase pairs (Mbp) on three human chromosomes. The DNA sequences were specifically labeled by fluorescence in situ hybridization. The relationship between mean-square interphase distance and genomic separation has two linear phases, with a transition at N2 Mbp. This biphasic relationship indicates the existence of two organizational levels at scales >100 kbp. On one level, chromatin appears to be arranged in large loops several Mbp in size. Within each loop, chromatin is randomly folded. On the second level, specific loop-attachment sites are arranged to form a supple, backbonelike structure, which also shows characteristic random walk behavior. This random walk/giant loop model is the simplest model that fully describes the observed large-scale spatial relationships. Additional evidence for large loops comes from measurements among probes in Xq28, where interphase distance increases and then locally decreases with increasing genomic separation. SIaORXLY after cell division, the mitotic chromosomes decondense and diffuse into the interphase nucleus. While individual chromosomes cannot be discerned, important processes related to chromosome function take place. Regulatory factors interact with chromatin, DNA is made accessible for transcription, RNA is produced and processed, DNA is replicated, and repairs are made of DNA strand breaks. When the chromosomes reappear for the next mitosis, they have been duplicated and prepared for rapid partitioning over the daughter cells. The complexity of these processes raises many questions about the large-scale organization of chromosomes and how this organization relates to cell function (e.g., Blobel, 1985;Manuelidis and Chen, 1990;Cook, 1991;Lawrence and Singer, 1991;De Boni, 1994).Diverse models, ranging from highly random to highly organized, have been proposed for the higher-order organization of interphase chromatin. These models variously involve irregularly folded fibers (DuPraw, 1965), radial loop structures (Manuelidis and Chen, 1990), giant loops (Ostashevsky and Lange, 1994), semirigid orientation ("Rabl" configuration) (Rabl, 1885;Comings, 1968), or random polymers confined by tethering or external forces (Hahnfeldt et al., 1993). Some models assign to chromo-

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mentioning

confidence: 99%

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

Engh

Hearst

et al. 1995

The Journal of Cell Biology

Self Cite

272

201

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“…Several models of higher-order chromatin structures have been proposed based on microscopic investigation of human interphase chromosomes (2,15,(35)(36)(37)(38). Chromosomes occupy a discrete territory, within which compact chromatin domains are distinguishable from less condensed ones (2,39,40).…”

Section: Discussionmentioning

confidence: 99%

Interphase chromosomes in Arabidopsis are organized as well defined chromocenters from which euchromatin loops emanate

Fransz

Jong

Lysak

et al. 2002

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

433

443

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Heterochromatin in the model plant Arabidopsis thaliana is confined to small pericentromeric regions of all five chromosomes and to the nucleolus organizing regions. This clear differentiation makes it possible to study spatial arrangement and functional properties of individual chromatin domains in interphase nuclei. Here, we present the organization of Arabidopsis chromosomes in young parenchyma cells. Heterochromatin segments are organized as condensed chromocenters (CCs), which contain heavily methylated, mostly repetitive DNA sequences. In contrast, euchromatin contains less methylated DNA and emanates from CCs as loops spanning 0.2-2 Mbp. These loops are rich in acetylated histones, whereas CCs contain less acetylated histones. We identified individual CCs and loops by fluorescence in situ hybridization by using rDNA clones and 131 bacterial artificial chromosome DNA clones from chromosome 4. CC and loops together form a chromosome territory. Homologous CCs and territories were associated frequently. Moreover, a considerable number of nuclei displayed perfect alignment of homologous subregions, suggesting physical transinteractions between the homologs. The arrangement of interphase chromosomes in Arabidopsis provides a well defined system to investigate chromatin organization and its role in epigenetic processes.

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“…Some recondensation of this region was then seen by day 10. The distribution of d values after day 2 conforms to a Rayleigh distribution (Sachs et al 1995) (SD/〈d〉 = 0.56 and median/〈d〉 = 0.9) indicating that the decondensed chromatin describes a random walk path.…”

Section: Chromatin Decondensation At Hoxbmentioning

confidence: 99%

Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription

Chambeyron

Bickmore²

2004

Genes Dev.

604

567

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The colinearity of genes in Hox clusters suggests a role for chromosome structure in gene regulation. We reveal programmed changes in chromatin structure and nuclear organization upon induction of Hoxb expression by retinoic acid. There is an early increase in the histone modifications that are marks of active chromatin at both the early expressed gene Hoxb1, and also at Hoxb9 that is not expressed until much later. There is also a visible decondensation of the chromatin between Hoxb1 and Hoxb9 at this early stage. However, a further change in higher-order chromatin structure, looping out of genes from the chromosome territory, occurs in synchrony with the execution of the gene expression program. We suggest that higher-order chromatin structure regulates the expression of the HoxB cluster at several levels. Locus-wide changes in chromatin structure (histone modification and chromatin decondensation) may establish a transcriptionally poised state but are not sufficient for the temporal program of gene expression. The choreographed looping out of decondensed chromatin from chromosome territories may then allow for activation of high levels of transcription from the sequence of genes along the cluster.

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A random-walk/giant-loop model for interphase chromosomes.

Cited by 283 publications

References 11 publications

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

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

Interphase chromosomes in Arabidopsis are organized as well defined chromocenters from which euchromatin loops emanate

Chromatin decondensation and nuclear reorganization of the HoxB locus upon induction of transcription

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