A pathway for mitotic chromosome formation

Gibcus, Johan H.; Samejima, Kumiko; Goloborodko, Anton; Samejima, Itaru; Naumova, Natalia; Nuebler, Johannes; Kanemaki, Masato T.; Xie, Linfeng; Paulson, James R.; Earnshaw, William C.; Mirny, Leonid A.; Dekker, Job

doi:10.1126/science.aao6135

Cited by 670 publications

(1,018 citation statements)

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“…A conceivable mechanism for lengthwise compaction is progressive “extrusion” of chromatin loops by condensins (Marko, 2011, Alipour and Marko, 2012, Marko, 2009, Nasmyth, 2001, Goloborodko et al, 2016a, Goloborodko et al, 2016b, Gibcus et al, 2018, Ganji et al, 2018). In such a model, condensin II would act to push chromatin to the exterior of the chromosome, perhaps in concert with condensin-associated factors such as the chromokinesin KIF4, (Samejima et al, 2012), with crowding of chromatin loops providing a thermodynamic drive for topo II to remove interlocks between different chromatids and chromosome.…”

Section: Discussionmentioning

confidence: 99%

Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold

et al. 2018

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During cell division, chromosomes must be folded into their compact mitotic form to ensure their segregation. This process is thought to be largely controlled by the action of condensin SMC protein complexes on chromatin fibers. However, how condensins organize metaphase chromosomes is not understood. We have combined micromanipulation of single human mitotic chromosomes, sub-nanonewton force measurement, siRNA interference of condensin subunit expression, and fluorescence microscopy, to analyze the role of condensin in large-scale chromosome organization. Condensin depletion leads to a dramatic (~ 10-fold) reduction in chromosome elastic stiffness relative to the native, non-depleted case. We also find that prolonged metaphase stalling of cells leads to overloading of chromosomes with condensin, with abnormally high chromosome stiffness. These results demonstrate that condensin is a main element controlling the stiffness of mitotic chromosomes. Isolated, slightly stretched chromosomes display a discontinuous condensing staining pattern, suggesting that condensins organize mitotic chromosomes by forming isolated compaction centers that do not form a continuous scaffold.

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Section: Discussionmentioning

confidence: 99%

Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold

et al. 2018

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“…Recently, Hi-C results obtained with mitotic cells were modeled using polymer-based simulations of chromatin structure, and it was proposed that chromatin in mitotic chromosomes is folded as a compact array of many loops having different sizes during mitosis (Gibcus et al, 2018). For chromatids with a radius of~0.36 lm (Gibcus et al, 2018), this linear density corresponds to~150 Mb/lm 3 . For chromatids with a radius of~0.36 lm (Gibcus et al, 2018), this linear density corresponds to~150 Mb/lm 3 .…”

Section: Of 12mentioning

confidence: 99%

“…In vitro experiments showed that the compaction degree of the chromatin filament is extremely dependent on ionic conditions (Daban, 2011;Collepardo-Guevara & Schlick, 2012;Grigoryev & Woodcock, 2012;Luger et al, 2012;Rippe, 2012;Boulé et al, 2015). The analysis of chromosomes in different condensation stages indicated a hierarchical folding of fibers having diameters from 30 to 250 nm (Kireeva et al, 2004), and studies of chromosome conformation capture suggested that mitotic chromosomes are formed by a compact array of chromatin loops (Gibcus et al, 2018). Several structural models have been proposed for the organization of chromatin in metaphase chromosomes.…”

Section: Introductionmentioning

confidence: 99%

Frozen‐hydrated chromatin from metaphase chromosomes has an interdigitated multilayer structure

et al. 2019

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Cryo‐electron tomography and small‐angle X‐ray scattering were used to investigate the chromatin folding in metaphase chromosomes. The tomographic 3D reconstructions show that frozen‐hydrated chromatin emanated from chromosomes is planar and forms multilayered plates. The layer thickness was measured accounting for the contrast transfer function fringes at the plate edges, yielding a width of ~ 7.5 nm, which is compatible with the dimensions of a monolayer of nucleosomes slightly tilted with respect to the layer surface. Individual nucleosomes are visible decorating distorted plates, but typical plates are very dense and nucleosomes are not identifiable as individual units, indicating that they are tightly packed. Two layers in contact are ~ 13 nm thick, which is thinner than the sum of two independent layers, suggesting that nucleosomes in the layers interdigitate. X‐ray scattering of whole chromosomes shows a main scattering peak at ~ 6 nm, which can be correlated with the distance between layers and between interdigitating nucleosomes interacting through their faces. These observations support a model where compact chromosomes are composed of many chromatin layers stacked along the chromosome axis.

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“…Moreover, it fails to form a cyclic trajectory. [18] In brief, CDD captures contact probability profile, PCC and Ins record higher-order structural properties, and MCM suggests macro information of genomic architecture. PCC representing loop signal possesses abundant cell-cycle information to distinguish cells at different phases, but there are many outliers which are significantly deviated from original phases (Figure 2A,B).…”

Section: The Reconstructed Trajectories Of Four Individual Feature Sementioning

confidence: 99%

Circular Trajectory Reconstruction Uncovers Cell‐Cycle Progression and Regulatory Dynamics from Single‐Cell Hi‐C Maps

Gao

Zhang

2019

Advanced Science

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Single‐cell Hi‐C technology is emerging and will provide unprecedented opportunities to elucidate chromosomal dynamics with high resolution. How to characterize pseudo time‐series of single cells using single‐cell Hi‐C maps is an essential and challenging topic. To this end, a powerful circular trajectory reconstruction tool CIRCLET is developed to resolve cell cycle phases of single cells by considering multiscale features of chromosomal architectures without specifying a starting cell. CIRCLET reveals its best superiority based on the combination of one feature set about global information and another two feature sets about local interactional information in terms of designed evaluation indexes and verification strategies from a collection of cell‐cycle Hi‐C maps of 1171 single cells. Further division of the reconstructed trajectory into 12 stages helps to accurately characterize the dynamics of chromosomal structures and explain the special regulatory events along cell‐cycle progression. Last but not the least, the reconstructed trajectory helps to uncover important regulatory genes related with dynamic substructures, providing a novel framework for discovering regulatory regions even cancer markers at single‐cell resolution.

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A pathway for mitotic chromosome formation

Cited by 670 publications

References 100 publications

Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold

Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold

Frozen‐hydrated chromatin from metaphase chromosomes has an interdigitated multilayer structure

Circular Trajectory Reconstruction Uncovers Cell‐Cycle Progression and Regulatory Dynamics from Single‐Cell Hi‐C Maps

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