Chromatin Dynamics

Hübner, Michael R; Spector, David L.

doi:10.1146/annurev.biophys.093008.131348

Cited by 155 publications

(147 citation statements)

References 132 publications

(147 reference statements)

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“…Interestingly, the A compartment tends to be less densely packed and to lie at the periphery of the chromosome territory. These observations are consistent with the findings of prior studies using both microscopy and Hi-C (9,29,30). Notably, a control model composed of a simple self-avoiding homopolymer chain failed to exhibit any of these results and, instead, recapitulated the expected properties for an equilibrium globule ( Fig.…”

Section: Significancesupporting

confidence: 92%

Transferable model for chromosome architecture

Pierro

Zhang

Aiden

et al. 2016

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

334

346

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In vivo, the human genome folds into a characteristic ensemble of 3D structures. The mechanism driving the folding process remains unknown. We report a theoretical model for chromatin (Minimal Chromatin Model) that explains the folding of interphase chromosomes and generates chromosome conformations consistent with experimental data. The energy landscape of the model was derived by using the maximum entropy principle and relies on two experimentally derived inputs: a classification of loci into chromatin types and a catalog of the positions of chromatin loops. First, we trained our energy function using the Hi-C contact map of chromosome 10 from human GM12878 lymphoblastoid cells. Then, we used the model to perform molecular dynamics simulations producing an ensemble of 3D structures for all GM12878 autosomes. Finally, we used these 3D structures to generate contact maps. We found that simulated contact maps closely agree with experimental results for all GM12878 autosomes. The ensemble of structures resulting from these simulations exhibited unknotted chromosomes, phase separation of chromatin types, and a tendency for open chromatin to lie at the periphery of chromosome territories.human genome | genome architecture | maximum entropy | molecular dynamics | Hi-C C hromatin comprises a highly flexible polymer composed of nucleosomes, DNA wrapped around histone proteins, connected to one another by a linker region of 20-50 bp. Hundreds of associated structural and regulatory proteins interact with the genetic material, coordinating the way chromatin folds to fit inside the nucleus of eukaryotic cells.The resulting ensemble of partially organized structures brings sections of DNA separated by a great genomic distance into close spatial proximity, and plays an important role in controlling gene transcription (1, 2). Although some of the features of this ensemble can be explained using simple polymer physics (3-6), there is now ample evidence that specific biochemical interactions play a crucial role (7-10). Understanding the interplay between biochemistry, genome architecture, and transcriptional regulation is a major outstanding challenge.For over two decades, molecular biology techniques that combine chromatin fragmentation and proximity ligation have given us quantitative information about how chromatin is organized in vivo (5,(11)(12)(13). In recent years, Hi-C experiments have made it possible to measure the frequency of contact between all pairs of genomic loci using a single experiment.Here, we explore a physical model by which local interactions between genomic loci can lead to the conformations of human chromosomes in interphase. Specifically, we propose a theoretical energy landscape model for chromatin folding, designated the Minimal Chromatin Model (MiChroM), which uses the maximum entropy principle (14, 15) in combination with a minimal number of assumptions to model the structural consequences of the aforementioned biochemical interactions. Importantly, MiChroM can be used to model biochemical inter...

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Section: Significancesupporting

confidence: 92%

Transferable model for chromosome architecture

Pierro

Zhang

Aiden

et al. 2016

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

334

346

View full text Add to dashboard Cite

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“…Both the tracking over 7.5 min and the xt and yt orthogonal portrayal of the movements are shown. (E) The movement of a given focus was analyzed by mean squared displacement (MSD) analysis (see formula in E), which yields both the diffusion coefficient and the radius of constraint (Rc = 0.6 mm) (Gasser 2002;Marshall 2002;Hubner and Spector 2010). Movement of the LYS2 chromosomal locus (black) is not quite identical to the constrained random walk modeled using averaged parameters of step size and movement from actual movement analysis (red).…”

Section: Dna-based Compartmentsmentioning

confidence: 99%

“…An excised ring of chromatin explores the entire nuclear volume in random walk (Rc = 0.9 mm) ( Figure 3) while a chromosomal locus moves in a constant, near-random walk within a radius of 0.5-0.7 mm (reviewed in Gasser 2002;Marshall 2002;Hubner and Spector 2010). For a yeast nucleus of 2 mm in diameter, this means that a chromosomal locus can explore 30% of the nuclear volume , whereas the same movement in a mammalian nucleus corresponds to ,1% of nuclear volume (Figure 3).…”

Section: Mechanisms Of Chromatin Movementmentioning

confidence: 99%

Structure and Function in the Budding Yeast Nucleus

2012

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Budding yeast, like other eukaryotes, carries its genetic information on chromosomes that are sequestered from other cellular constituents by a double membrane, which forms the nucleus. An elaborate molecular machinery forms large pores that span the double membrane and regulate the traffic of macromolecules into and out of the nucleus. In multicellular eukaryotes, an intermediate filament meshwork formed of lamin proteins bridges from pore to pore and helps the nucleus reform after mitosis. Yeast, however, lacks lamins, and the nuclear envelope is not disrupted during yeast mitosis. The mitotic spindle nucleates from the nucleoplasmic face of the spindle pole body, which is embedded in the nuclear envelope. Surprisingly, the kinetochores remain attached to short microtubules throughout interphase, influencing the position of centromeres in the interphase nucleus, and telomeres are found clustered in foci at the nuclear periphery. In addition to this chromosomal organization, the yeast nucleus is functionally compartmentalized to allow efficient gene expression, repression, RNA processing, genomic replication, and repair. The formation of functional subcompartments is achieved in the nucleus without intranuclear membranes and depends instead on sequence elements, protein-protein interactions, specific anchorage sites at the nuclear envelope or at pores, and long-range contacts between specific chromosomal loci, such as telomeres. Here we review the spatial organization of the budding yeast nucleus, the proteins involved in forming nuclear subcompartments, and evidence suggesting that the spatial organization of the nucleus is important for nuclear function. TABLE OF CONTENTS Abstract 107Introduction 108

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“…[1][2][3] Those factors impact the distribution and condensation of chromatin fiber (DNA in complex with histone proteins). Consequently, chromatin may exist in relaxed (euchromatin) or compacted (heterochromatin) state, 4 depending on both genetic and epigenetic regulation.…”

Section: Introductionmentioning

confidence: 99%

Spatial relationship between chromosomal domains in diploid and autotetraploidArabidopsis thaliananuclei

Sas–Nowosielska

Bernaś

2016

Nucleus

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Polyploids constitute more than 80% of angiosperm plant species. Their DNA content is often further increased by endoreplication, which occurs as a part of cell differentiation. Here, we explore the relationship between 3D chromatin architecture, number of genome copies and their origin in the model plant, Arabidopsis thaliana. Spatial proximity between pericentromeric, interstitial and subtelomeric domains of chromosomes 1 and 4 was quantified over a range of distances. The results indicate that average nuclear volume as well as chromatin density increase with the genome copy number. Similar dependence is observed when association of homologous chromosomes (in 2C/ endopolyploid nuclei) and sister chromatid separation (in endopolyploid nuclei) is studied. Moreover, clusters of chromosomal domains are detectable at the spatial scale above microscopy resolution. Subtelomeric, interstitial and pericentromeric chromosomal domains are affected to different extent by these processes, which are modulated by endopolyploidy. This factor influences fusion of heterochromatin as well. Nonetheless, local chromatin architecture of Arabidopsis thaliana depends mainly on endopolyploidy level, and to lesser extend on polyploidy.

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Chromatin Dynamics

Cited by 155 publications

References 132 publications

Transferable model for chromosome architecture

Transferable model for chromosome architecture

Structure and Function in the Budding Yeast Nucleus

Spatial relationship between chromosomal domains in diploid and autotetraploidArabidopsis thaliananuclei

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