A Polymer Model for the Structural Organization of Chromatin Loops and Minibands in Interphase Chromosomes

Ostashevsky, Joseph Y.

doi:10.1091/mbc.9.11.3031

Cited by 56 publications

(48 citation statements)

References 62 publications

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“…The lack of stationary replication origins allows constant change of mutational biases resulting in high compositional variability. Conversely, compositional properties of the genome probably dictate the higher order chromatin structure (Ostashevsky 1998) and therefore it is difficult to establish a clear cause/effect relationship between the replication process and compositional properties of the genome. Because these speculations are based largely on the lack of information concerning the mechanism of eukaryotic replication, empirical data is required to test their validity.…”

Section: Yeast Versus Multicellular Eukaryotes: a Possible Relationshmentioning

confidence: 99%

Assessment of Compositional Heterogeneity Within and Between Eukaryotic Genomes

Nekrutenko

2000

Genome Research

135

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Using large amounts of long genomic sequences, we studied the compositional patterns of eukaryotic genomes. We developed a simple measure, the compositional heterogeneity (or variability) index, to compare the differences in compositional heterogeneity between long genomic sequences. The index measures the average difference in GC content between two adjacent windows normalized by the standard error expected under the assumption of random distribution of nucleotides in a window. We report the following findings: (1) The extent of the compositional heterogeneity in a genomic sequence strongly correlates with its GC content in all multicellular eukaryotes studied regardless of genome size. (2) The human genome appears to be highly compositionally heterogeneous both within and between individual chromosomes; the heterogeneity goes much beyond the predictions of the isochore model. (3) All genomes of multicellular eukaryotes examined in this study are compositionally heterogeneous, although they also contain compositionally uniform segments, or isochores. (4) The true uniqueness of the human (or mammalian) genome is the presence of very high GC regions, which exhibit unusually high compositional heterogeneity and contain few long homogeneous segments (isochores). In general, GC-poor isochores tend to be longer than GC-rich ones. These findings indicate that the genomes of multicellular organisms are much more heterogeneous in nucleotide composition than depicted by the isochore model and so lead to a looser definition of isochores.

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Section: Yeast Versus Multicellular Eukaryotes: a Possible Relationshmentioning

confidence: 99%

Assessment of Compositional Heterogeneity Within and Between Eukaryotic Genomes

Nekrutenko

2000

Genome Research

135

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“…Recent evidence suggests that interphase chromatin is organized in large loops, several megabase pair in size Yokota et al, 1995;Ostashevsky, 1998). While within each loop chromatin is randomly folded, specific loop-attachment sites may impose a constrained backbone structure (Yokota et al, 1995;Marshall et al, 1997;Ostashevsky, 1998Ostashevsky, , 2000Cremer et al, 2000).At present, it is well established that both mitotic chromosomes and interphase chromatin are composed of distinct functional domains (for recent reviews, see Cockell and Gasser, 1999;Belmont et al, 1999;Cremer et al, 2000). Each domain occupies a specific spatial position and replicates at a precise time during S phase.…”

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confidence: 99%

“…The rationale for this is that bands that are larger and/or closer to the centromere should exert more influence than smaller or more distant bands. We used the square root of the distance because of previous reports indicating a correlation between chromosomal genomic separation and mean-square interphase distance (Yokota et al, 1995: Ostashevsky, 1998.The results of a linear regression analysis of ␣-satellite DNA distribution against each isolated variable are depicted in Figure 3c. The variable with higher explanatory power is where fЈ stands for the linearized frequency (see MATERI-ALS AND METHODS).…”

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confidence: 99%

Chromosomal G-dark Bands Determine the Spatial Organization of Centromeric Heterochromatin in the Nucleus

Carvalho

Pereira

Ferreira

et al. 2001

MBoC

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Gene expression can be silenced by proximity to heterochromatin blocks containing centromeric ␣-satellite DNA. This has been shown experimentally through cis-acting chromosome rearrangements resulting in linear genomic proximity, or through trans-acting changes resulting in intranuclear spatial proximity. Although it has long been been established that centromeres are nonrandomly distributed during interphase, little is known of what determines the three-dimensional organization of these silencing domains in the nucleus. Here, we propose a model that predicts the intranuclear positioning of centromeric heterochromatin for each individual chromosome. With the use of fluorescence in situ hybridization and confocal microscopy, we show that the distribution of centromeric ␣-satellite DNA in human lymphoid cells synchronized at G 0 /G 1 is unique for most individual chromosomes. Regression analysis reveals a tight correlation between nuclear distribution of centromeric ␣-satellite DNA and the presence of G-dark bands in the corresponding chromosome. Centromeres surrounded by G-dark bands are preferentially located at the nuclear periphery, whereas centromeres of chromosomes with a lower content of G-dark bands tend to be localized at the nucleolus. Consistent with the model, a t(11; 14) translocation that removes G-dark bands from chromosome 11 causes a repositioning of the centromere, which becomes less frequently localized at the nuclear periphery and more frequently associated with the nucleolus. The data suggest that "chromosomal environment" plays a key role in the intranuclear organization of centromeric heterochromatin. Our model further predicts that facultative heterochromatinization of distinct genomic regions may contribute to cell-type specific patterns of centromere localization. INTRODUCTIONHow are genomes organized in the nucleus, and what is the role of genome organization on cellular functions? These fundamental questions in cell biology are attracting increased attention as the genomes of higher eukaryotes are being sequenced. Diverse models, ranging from highly random to highly organized, have been proposed for the organization of interphase chromatin (for reviews see Manuelidis, 1990;Haaf and Schmid, 1991;Cremer et al., 1993). Recent evidence suggests that interphase chromatin is organized in large loops, several megabase pair in size Yokota et al., 1995;Ostashevsky, 1998). While within each loop chromatin is randomly folded, specific loop-attachment sites may impose a constrained backbone structure (Yokota et al., 1995;Marshall et al., 1997;Ostashevsky, 1998Ostashevsky, , 2000Cremer et al., 2000).At present, it is well established that both mitotic chromosomes and interphase chromatin are composed of distinct functional domains (for recent reviews, see Cockell and Gasser, 1999;Belmont et al., 1999;Cremer et al., 2000). Each domain occupies a specific spatial position and replicates at a precise time during S phase. In metaphase chromosomes, the domains are identified as alternate transverse bands...

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“…Whether you associate the different polymer blocks with GC rich and AT rich regions [18] or with other chromatin characteristics is not of primary importance for our model. A multiblock copolymer containing two alternately located types of blocks can form a single-chain string of loop clusters called micelles [29].…”

Section: The Biological Modelmentioning

confidence: 99%

“…Adjacent rosettes are connected by chromatin linker segments with the same DNA content as one loop. Approaches based on the isochore model also predict the formation of rosettes of about 1 Mbp [18].…”

Section: Introductionmentioning

confidence: 96%

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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A Polymer Model for the Structural Organization of Chromatin Loops and Minibands in Interphase Chromosomes

Cited by 56 publications

References 62 publications

Assessment of Compositional Heterogeneity Within and Between Eukaryotic Genomes

Assessment of Compositional Heterogeneity Within and Between Eukaryotic Genomes

Chromosomal G-dark Bands Determine the Spatial Organization of Centromeric Heterochromatin in the Nucleus

Dynamic Simulation of Active/Inactive Chromatin Domains

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