ChromoShake: a chromosome dynamics simulator reveals that chromatin loops stiffen centromeric chromatin

Lawrimore, Josh; Aicher, Joseph K.; Hahn, Patrick J.; Fulp, Alyona; Kompa, Ben; Vicci, Leandra; Falvo, Michael R.; Taylor, Russell M.; Bloom, Kerry

doi:10.1091/mbc.e15-08-0575

Cited by 40 publications

(94 citation statements)

References 42 publications

(67 reference statements)

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“…Loops that are approx. 10 kb give rise to a cohesin barrel that matches the dimension and homogeneity found in vivo (Lawrimore et al 2016). The size of these loops is comparable to the 5 kb chromosome interaction domains found in yeast from Micro-C (Hsieh et al 2015).…”

Section: Characteristics Of Centromere Chromatin—primary Folding Of Asupporting

confidence: 60%

“…The size of the loops can be estimated from the region over which the structural maintenance of chromosome proteins (SMC’s cohesin and condensin) are enriched. Loops from each chromosome are in turn looped, adopting loops within loop organization (Lawrimore et al 2016) (Fig. 2).…”

Section: Characteristics Of Centromere Chromatin—primary Folding Of Amentioning

confidence: 99%

“…The size and number of secondary loops has been estimated through the use of a chromosome dynamics simulator (Lawrimore et al 2016). The bead-spring polymer model finds the thermodynamically favorable state of a string of beads with hinge forces connecting the beads tuned to give the strand the bending rigidity determined for DNA.…”

Section: Characteristics Of Centromere Chromatin—primary Folding Of Amentioning

confidence: 99%

“…Furthermore, the radial distance of cohesin from the spindle, as well as the homogeneity of the barrel demands a physical explanation. Rather than holding sister chromatids in the pericentromere, intra-chromatid linkages as proposed in Lawrimore et al (2016) account for the position and dynamics of pericentric cohesin. Behavior of the centromere linked lacO array as it extends and retracts thermodynamically, as well as in response to MT pulling and pushing forces also favors intra-chromosomal loops diagrammed in the model shown in Fig.…”

Section: Characteristics Of Centromere Chromatin—primary Folding Of Amentioning

confidence: 99%

“…2. The intra-chromatid linkages contribute to the pushing mechanism predicted from the bottle brush, providing a novel view of centromere function in promoting sister separation and kinetochore tension at the metaphase plate (Lawrimore et al 2015, 2016). Whether non-sister chromosome interactions are mediated by cohesin within the pericentromere remain controversial.…”

Section: Characteristics Of Centromere Chromatin—primary Folding Of Amentioning

confidence: 99%

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Centromere Structure and Function

Bloom

Costanzo

2017

Progress in Molecular and Subcellular Biology

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The centromere is the genetic locus that specifies the site of kinetochore assembly, where the chromosome will attach to the kinetochore microtubule. The pericentromere is the physical region responsible for the geometry of bi-oriented sister kinetochores in metaphase. In budding yeast the 125 bp point centromere is sufficient to specify kinetochore assembly. The flanking region is enriched (3X) in cohesin and condensin relative to the remaining chromosome arms. The enrichment spans about 30-50 kb around each centromere. We refer to the flanking chromatin as the pericentromere in yeast. In mammals, a 5-10 Mb region dictates where the kinetochore is built. The kinetochore interacts with a very small fraction of DNA on the surface of the centromeric region. The remainder of the centromere lies between the sister kinetochores. This is typically called centromere chromatin. The chromatin sites that directly interface to microtubules cannot be identified due to the repeated sequence within the mammalian centromere. However in both yeast and mammals, the total amount of DNA between the sites of microtubule attachment in metaphase is highly conserved. In yeast the 16 chromosomes are clustered into a 250 nm diameter region, and 800 kb (16 × 50 kb) or ~1 Mb of DNA lies between sister kinetochores. In mammals, 5-10 Mb lies between sister kinetochores. In both organisms the sister kinetochores are separated by about 1 μm. Thus, centromeres of different organisms differ in how they specify kinetochore assembly, but there may be important centromere chromatin functions that are conserved throughout phylogeny. Recently, centromeric chromatin has been reconstituted in vitro using alpha satellite DNA revealing unexpected features of centromeric DNA organization, replication, and response to stress. We will focus on the conserved features of centromere in this review.

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Section: Characteristics Of Centromere Chromatin—primary Folding Of Asupporting

confidence: 60%

Section: Characteristics Of Centromere Chromatin—primary Folding Of Amentioning

confidence: 99%

Section: Characteristics Of Centromere Chromatin—primary Folding Of Amentioning

confidence: 99%

Section: Characteristics Of Centromere Chromatin—primary Folding Of Amentioning

confidence: 99%

Section: Characteristics Of Centromere Chromatin—primary Folding Of Amentioning

confidence: 99%

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Centromere Structure and Function

Bloom

Costanzo

2017

Progress in Molecular and Subcellular Biology

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Tension sensors reveal how the kinetochore shares its load

Salmon

Bloom

2017

BioEssays

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At metaphase in mitotic cells, pulling forces at the kinetochore-microtubule interface create tension by stretching the centromeric chromatin between oppositely oriented sister kinetochores. This tension is important for stabilizing the end-on kinetochore microtubule attachment required for proper bi-orientation of sister chromosomes as well as for satisfaction of the Spindle Assembly Checkpoint and entry into anaphase. How force is coupled by proteins to kinetochore microtubules and resisted by centromere stretch is becoming better understood as many of the proteins involved have been identified. Recent application of genetically encoded fluorescent tension sensors within the mechanical linkage between the centromere and kinetochore microtubules are beginning to reveal – from live cell assays – protein specific contributions that are functionally important.

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Three-Dimensional Thermodynamic Simulation of Condensin as a DNA-Based Translocase

Lawrimore

Forest

et al. 2019

Methods in Molecular Biology

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Chromatin dynamics and organization can be altered by condensin complexes. In turn, the molecular behavior of a condensin complex changes based on the tension of the substrate to which condensin is bound. This interplay between chromatin organization and condensin behavior demonstrates the need for tools that allows condensin complexes to be observed on a variety of chromatin organizations. We provide a method for simulating condensin complexes on a dynamic polymer substrate using the polymer dynamics simulator ChromoShake and the condensin simulator RotoStep. These simulations can be converted into simulated fluorescent images that are able to be directly compared to experimental images of condensin and fluorescently labeled chromatin. Our pipeline enables users to explore how changes in condensin behavior alters chromatin dynamics and vice versa while providing simulated image datasets that can be directly compared to experimental observations.

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ChromoShake: a chromosome dynamics simulator reveals that chromatin loops stiffen centromeric chromatin

Abstract: A novel chromosome simulator recapitulates the position and dynamics of centromeric chromatin in a model composed of cross-linked intramolecular loops. Simulations reveal that chromatin loops stiffen the centromere and dictate the distribution of pericentric cohesin.

Cited by 40 publications

References 42 publications

Centromere Structure and Function

Centromere Structure and Function

Tension sensors reveal how the kinetochore shares its load

Three-Dimensional Thermodynamic Simulation of Condensin as a DNA-Based Translocase

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