Centromere Tethering Confines Chromosome Domains

Verdaasdonk, Jolien S.; Vasquez, Paula A.; Barry, Raymond Mario; Barry, Terence P.; Goodwin, Scott C.; Forest, M. Gregory; Bloom, Kerry

doi:10.1016/j.molcel.2013.10.021

Cited by 91 publications

(173 citation statements)

References 58 publications

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“…During the G1 stage of the cell cycle, subtelomeres localize principally at the nuclear periphery, centromeres are tethered to the SPB through nuclear microtubules and internal loci are preferentially found in the nuclear interior (Bystricky et al, 2005;Jin et al, 1998;Schober et al, 2008;Therizols et al, 2010;Verdaasdonk et al, 2013;Wong et al, 2012). We show that during G1, the motion of subtelomeric, peri-centromeric and interstitial loci is subdiffusive (exponent α≈0.5).…”

Section: Interphase Subdiffusive Chromatin Dynamics Requires Actinmentioning

confidence: 64%

Evidence for actin dual role in regulating chromosome organization and dynamics in yeast

Spichal

Brion

Herbert

et al. 2016

Journal of Cell Science

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Eukaryotic chromosomes undergo movements that are involved in the regulation of functional processes such as DNA repair. To better understand the origin of these movements, we used fluorescence microscopy, image analysis and chromosome conformation capture to quantify the actin contribution to chromosome movements and interactions in budding yeast. We show that both the cytoskeletal and nuclear actin drive local chromosome movements, independently of Csm4, a putative LINC protein. Inhibition of actin polymerization reduces subtelomere dynamics, resulting in more confined territories and enrichment in subtelomeric contacts. Artificial tethering of actin to nuclear pores increased both nuclear pore complex (NPC) and subtelomere motion. Chromosome loci that were positioned away from telomeres exhibited reduced motion in the presence of an actin polymerization inhibitor but were unaffected by the lack of Csm4. We further show that actin was required for locus mobility that was induced by targeting the chromatin-remodeling protein Ino80. Correlated with this, DNA repair by homologous recombination was less efficient. Overall, interphase chromosome dynamics are modulated by the additive effects of cytoskeletal actin through forces mediated by the nuclear envelope and nuclear actin, probably through the function of actin in chromatin-remodeling complexes.

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Section: Interphase Subdiffusive Chromatin Dynamics Requires Actinmentioning

confidence: 64%

Evidence for actin dual role in regulating chromosome organization and dynamics in yeast

Spichal

Brion

Herbert

et al. 2016

Journal of Cell Science

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“…Elastic dynamics of fluctuating chromosomal loci were observed not only in different bacteria (31) (Fig. S1C), but also in eukaryotic nuclei by tracking fluorescently labeled chromosomal loci (59). Therefore, these elastic dynamics likely represent a universal feature of compacted, high-order structured DNA.…”

Section: Discussionmentioning

confidence: 89%

DNA-relay mechanism is sufficient to explain ParA-dependent intracellular transport and patterning of single and multiple cargos

Surovtsev

Campos

Jacobs‐Wagner

2016

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

121

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Spatial ordering of macromolecular components inside cells is important for cellular physiology and replication. In bacteria, ParA/B systems are known to generate various intracellular patterns that underlie the transport and partitioning of low-copy-number cargos such as plasmids. ParA/B systems consist of ParA, an ATPase that dimerizes and binds DNA upon ATP binding, and ParB, a protein that binds the cargo and stimulates ParA ATPase activity. Inside cells, ParA is asymmetrically distributed, forming a propagating wave that is followed by the ParB-rich cargo. These correlated dynamics lead to cargo oscillation or equidistant spacing over the nucleoid depending on whether the cargo is in single or multiple copies. Currently, there is no model that explains how these different spatial patterns arise and relate to each other. Here, we test a simple DNArelay model that has no imposed asymmetry and that only considers the ParA/ParB biochemistry and the known fluctuating and elastic dynamics of chromosomal loci. Stochastic simulations with experimentally derived parameters demonstrate that this model is sufficient to reproduce the signature patterns of ParA/B systems: the propagating ParA gradient correlated with the cargo dynamics, the single-cargo oscillatory motion, and the multicargo equidistant patterning. Stochasticity of ATP hydrolysis breaks the initial symmetry in ParA distribution, resulting in imbalance of elastic force acting on the cargo. Our results may apply beyond ParA/B systems as they reveal how a minimal system of two players, one binding to DNA and the other modulating this binding, can transform directionally random DNA fluctuations into directed motion and intracellular patterning. intracellular patterning | active transport | ParA/B system | partitioning | mathematical model S patial patterns are omnipresent in biology, spanning a wide range of size scales and organizational levels. At the singlecell level, spatial patterns are readily apparent in the formation of protein gradients and the regular arrangement of cytoskeletal structures, macromolecular complexes, and organelles. Intracellular patterning serves important functions, as it provides a means for cells to organize their intracellular space, sense their geometry, and partition their cellular content (1-5). However, the mechanisms that drive intracellular patterning are often poorly understood.In this study, we aimed to understand how spatial patterns driven by bacterial ParA/B systems can arise within a small (micrometer-scale) intracellular space dominated by fluctuations and diffusion. ParA/B systems consist of only two proteins, ParA and ParB, that drive the transport and equipartitioning of lowcopy-number macromolecular complexes, often referred to as cargos. ParA/B systems are widespread among bacteria (6). For example, many low-copy-number plasmids encode a ParA/B system that distributes plasmid copies at regular intervals along the cell length (7-10). This striking plasmid patterning ensures that division at midcell results in ...

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“…In yeast, computational studies have considered a range of models differing in the number of attachments they consider 11,12,14,15,17,18 . Homogeneous interaction models assume all chromosome sites interact equally with the NE due to the complete presence or absence of attachments at all sites along the chromosome fiber 17 .…”

Section: Introductionmentioning

confidence: 99%

“…Heterogeneous interaction models allow affinity for the NE to vary along the chromosome fiber; several Downloaded by [UQ Library] at 01: 10 15 June 2015 models have specifically investigated the effects of chromosome tethers positioned at the centromeres and telomeres 11,12,14,15,[17][18][19] . These studies in yeast have led to several predictions: the 3D position of a gene can be altered due to the presence of an NE tether positioned within 10 kb 11 ; removal of chromosomal tethers at the centromere increases chromosome mobility as quantified by its confinement radius 18 ; the presence of Chr-NE tethers affects the distribution of telomere-telomere distances 17 ; the position of chromosomes within the nucleus may be altered due to a combination of Chr-NE tethering and volume exclusion 12 ; and the distribution of distances between the spindle pole body and the silent mating locus depends on tethering at the telomere 11 .…”

Section: Introductionmentioning

confidence: 99%

Quantified effects of chromosome-nuclear envelope attachments on 3D organization of chromosomes

Kinney

Onufriev

Sharakhov

2015

Nucleus

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We use a combined experimental and computational approach to study the effects of chromosome-nuclear envelope (Chr-NE) attachments on the 3D genome organization of Drosophila melanogaster (fruit fly) salivary gland nuclei. We consider 3 distinct models: a Null model - without specific Chr-NE attachments, a 15-attachment model - with 15 previously known Chr-NE attachments, and a 48-attachment model - with 15 original and 33 recently identified Chr-NE attachments. The radial densities of chromosomes in the models are compared to the densities observed in 100 experimental images of optically sectioned salivary gland nuclei forming "z-stacks." Most of the experimental z-stacks support the Chr-NE 48-attachment model suggesting that as many as 48 chromosome loci with appreciable affinity for the NE are necessary to reproduce the experimentally observed distribution of chromosome density in fruit fly nuclei. Next, we investigate if and how the presence and the number of Chr-NE attachments affect several key characteristics of 3D genome organization: chromosome territories and gene-gene contacts. This analysis leads to novel insight about the possible role of Chr-NE attachments in regulating the genome architecture. Specifically, we find that model nuclei with more numerous Chr-NE attachments form more distinct chromosome territories and their chromosomes intertwine less frequently. Intra-chromosome and intra-arm contacts are more common in model nuclei with Chr-NE attachments compared to the Null model (no specific attachments), while inter-chromosome and inter-arm contacts are less common in nuclei with Chr-NE attachments. We demonstrate that Chr-NE attachments increase the specificity of long-range inter-chromosome and inter-arm contacts. The predicted effects of Chr-NE attachments are rationalized by intuitive volume vs. surface accessibility arguments.

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Centromere Tethering Confines Chromosome Domains

Cited by 91 publications

References 58 publications

Evidence for actin dual role in regulating chromosome organization and dynamics in yeast

Evidence for actin dual role in regulating chromosome organization and dynamics in yeast

DNA-relay mechanism is sufficient to explain ParA-dependent intracellular transport and patterning of single and multiple cargos

Quantified effects of chromosome-nuclear envelope attachments on 3D organization of chromosomes

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