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

Sun, Mingxuan; Biggs, Ronald; Hornick, Jessica E.; Marko, John F.

doi:10.1007/s10577-018-9584-1

Cited by 71 publications

(92 citation statements)

References 58 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Topo IIs allow passage of chromatin segments through one another, permitting chromosome topology to fluctuate [2]. However, Topo IIs cannot disentangle chromosomes by themselves [57][58][59][60], since they are unable to directly sense global chromosome topology. By allowing topology fluctuations, Topo II can maintain topological equilibrium, allowing disentanglement to occur gradually as lengthwise compaction proceeds.…”

Section: Discussionmentioning

confidence: 99%

Chromosome disentanglement driven via optimal compaction of loop-extruded brush structures

Brahmachari

Marko

2019

Preprint

Self Cite

View full text Add to dashboard Cite

Eukaryote cell division features a chromosome compaction-decompaction cycle that is synchronized with their physical and topological segregation. It has been proposed that lengthwise compaction of chromatin into mitotic chromosomes via loop extrusion underlies the compactionsegregation/resolution process. We analyze this disentanglement scheme via considering the chromosome to be a succession of DNA/chromatin loops -a polymer "brush" -where active extrusion of loops controls the brush structure. Given topoisomerase (TopoII)-catalyzed topology fluctuations, we find that inter-chromosome entanglements are minimized for a certain "optimal" loop that scales with the chromosome size. The optimal loop organization is in accord with experimental data across species, suggesting an important structural role of genomic loops in maintaining a less entangled genome. Application of the model to the interphase genome indicates that active loop extrusion can maintain a level of chromosome compaction with suppressed entanglements; the transition to the metaphase state requires higher lengthwise compaction, and drives complete topological segregation. Optimized genomic loops may provide a means for evolutionary propagation of gene-expression patterns while simultaneously maintaining a disentangled genome. We also find that compact metaphase chromosomes have a densely packed core along their cylindrical axes that explains their observed mechanical stiffness. Our model connects chromosome structural reorganization to topological resolution through the cell cycle, and highlights a mechanism of directing Topo-II mediated strand passage via loop extrusion driven lengthwise compaction.

show abstract

Section: Discussionmentioning

confidence: 99%

Chromosome disentanglement driven via optimal compaction of loop-extruded brush structures

Brahmachari

Marko

2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Older work has shown that condensin is responsible for about half of the spring constant of the kintetochore (Ribeiro et al, 2009). Recent work has shown that condensin is approximately linearly correlated to the stiffness of mitotic chromosomes (Sun et al, 2018), suggesting that most of the stiffness is governed by the chromatin loop-extruding elements, which are also apparently the primary crosslinking elements ( Figure 5A). Previous work has shown that DNA/chromatin constitutes the underlying connectivity of mitotic chromosomes, which makes up the underlying fiber (Poirier and Marko, 2002;Sun et al, 2011).…”

Section: Incorporating Chromatin Interactions Into the Model Of Mitotmentioning

confidence: 94%

“…Since condensin is the most well known contributor to chromosome strength, we sought to check whether levels of condensin on mitotic chromosomes increased when treated with MS. Previous work has shown that chromosome stiffness is approximately linearly proportional to the amount of condensin on the chromosome (Sun et al, 2018). We used antibodies against SMC2, a core subunit of condensin, to determine if there was a difference in fluorescence intensities between untreated and MS treated cells and captured chromosomes.…”

Section: Methylstat Treatment Does Not Change Smc2 Levelsmentioning

confidence: 99%

“…This suggests that histone PTMs and their changes in mitosis may intrinsically affect mitotic compaction through nucleosome-nucleosome interactions. Other experiments have shown that DNA forms the underlying connectivity of mitotic chromosomes (Poirier and Marko, 2002;Sun et al, 2011) and condensin in the central axis of mitotic chromosomes is discontiguous (Sun et al, 2018;Walther et al, 2018). While condensin provides the majority of the stiffness of mitotic chromosomes, it remains unclear how much chromatin-chromatin interactions could contribute to the stiffness of the mitotic chromosome.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of altering histone post-translational modifications on mitotic chromosome structure and mechanics

Biggs¹,

Stephens²,

Liu³

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

During cell division chromatin is compacted into mitotic chromosomes to aid faithful segregation of the genome between two daughter cells. Post-translational modifications (PTM) of histones alter compaction of interphase chromatin, but it remains poorly understood how these modifications affect mitotic chromosome stiffness and structure. Using micropipette-based force measurements and epigenetic drugs, we probed the influence of canonical histone PTMs that dictate interphase euchromatin (acetylation) and heterochromatin (methylation) on mitotic chromosome stiffness. By measuring chromosome doubling force (the force required to double chromosome length), we find that histone methylation, but not acetylation, contributes to mitotic structure and stiffness. We discuss our findings in the context of chromatin gel modeling of the large-scale organization of mitotic chromosomes.

show abstract

“…In cap-d3 mutants we observed chromocenter clustering but barely chromosome territory dispersion. During mitosis, CAP-D3 is needed to confer the rigidity of the chromosome arms (Green et al, 2012) and human condensin controls the elasticity of mitotic chromosomes (Sun et al, 2018). We suppose, that during interphase, CAP-D3 localizes in euchromatin, possibly along the euchromatic loops, mediating the rigidity which is needed to keep the chromocenters away from each other.…”

Section: Cap-d Proteins Prevent Heterochromatin Clusteringmentioning

confidence: 95%

The Arabidopsis condensin CAP-D subunits arrange interphase chromatin

Municio

Antosz

Grasser

et al. 2019

Preprint

View full text Add to dashboard Cite

Condensins are best known for their role in shaping chromosomes. However, other functions as organizing interphase chromatin and transcriptional control have been reported in yeasts and animals. Yeasts encode one condensin complex, while higher eukaryotes have two of them (condensin I and II). Both, condensin I and II, are conserved in Arabidopsis thaliana, but so far little is known about their function. Here we show that the A. thaliana CAP-D2 (condensin I) and CAP-D3 (condensin II) subunits are highly expressed in mitotically active tissues. In silico and pull-down experiments indicate that both CAP-D proteins interact with the other condensin I and II subunits. Our data suggest that the expression, localization and composition of the condensin complexes in A. thaliana are similar as in other higher eukaryotes. Previous experiments showed that the lack of A. thaliana CAP-D3 leads to centromere association during interphase. To study the function of CAP-D3 in chromatin organization more in detail we compared the nuclear distribution of rDNA, of centromeric chromocenters and of different epigenetic marks, as well as the nuclear size between wild-type and cap-d3 mutants. In these mutants an association of heterochromatic sequences occurs, but nuclear size and the general methylation and acetylation patterns remain unchanged. In addition, transcriptome analyses revealed a moderate influence of CAP-D3 on general transcription, but a stronger one on transcription of stress-related genes. We propose a model for the CAP-D3 function during interphase, where CAP-D3 localizes in euchromatin loops to stiff them, and consequently separates centromeric regions and 45S rDNA repeats.

show abstract

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

Cited by 71 publications

References 58 publications

Chromosome disentanglement driven via optimal compaction of loop-extruded brush structures

Chromosome disentanglement driven via optimal compaction of loop-extruded brush structures

Effects of altering histone post-translational modifications on mitotic chromosome structure and mechanics

The Arabidopsis condensin CAP-D subunits arrange interphase chromatin

Contact Info

Product

Resources

About