Compaction and segregation of sister chromatids via active loop extrusion

Goloborodko, Anton; Imakaev, Maxim; Marko, John F.; Mirny, Leonid A.

doi:10.7554/elife.14864

Cited by 280 publications

(227 citation statements)

References 65 publications

Supporting

Mentioning

201

Contrasting

Unclassified

Order By: Relevance

“…Loop extrusion has been hypothesized as a mechanism of chromosome compaction (69, 70) and most recently examined by simulations (25, 48, 71) and supported by single-molecule studies (72). In this process, each condensin starts forming a progressively larger loop until it dissociates or stops being blocked by neighboring condensins or other DNA-binding proteins.…”

Section: Discussionmentioning

confidence: 99%

A pathway for mitotic chromosome formation

Gibcus

Samejima

Goloborodko

et al. 2018

Science

Self Cite

651

106

871

View full text Add to dashboard Cite

Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C of synchronous DT40 cell cultures with polymer simulations. We show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner and arrays of consecutive 60 kb loops are formed. During prometaphase ~80 kb inner loops are nested within ~400 kb outer loops. The loop array acquires a helical arrangement with consecutive loops emanating from a central spiral-staircase condensin scaffold. The size of helical turns progressively increases during prometaphase to ~12 Mb. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins while condensin II is required for helical winding.

show abstract

Section: Discussionmentioning

confidence: 99%

A pathway for mitotic chromosome formation

Gibcus

Samejima

Goloborodko

et al. 2018

Science

Self Cite

651

106

871

View full text Add to dashboard Cite

show abstract

“…Note that other than these requirements, we allow positions of loops to be variable along the chromosome arm. In polymer simulations, intra-chromosomal loops are then imposed with harmonic bonds (as in 4,65 ).…”

Section: Methodsmentioning

confidence: 99%

SMC complexes differentially compact mitotic chromosomes according to genomic context

et al. 2017

Self Cite

View full text Add to dashboard Cite

Structural Maintenance of Chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modeling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids whilst condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes.

show abstract

“…2(Bii) form a "higher order" looped structure that is also commonly known as a "rosette" 40,41 or "transitive" loops 35 . This type of looped structure has been identified in the contact maps obtained from "Hi-C" 35 experiments on eukaryotic nuclei and it has been associated with the presence of transcription factories 42,43 and with other types of ATP-driven organisation of chromosomal domains in both, interphase and metaphase chromosomes 35,[44][45][46][47] . It is somewhat intriguing to find similar patterns in the much simpler case of a dense solution of ring polymers as the one studied in this work; in particular, it may suggest that these higherorder looped architectures may also be guided by entropic forces working alongside topological constraints (more on this in the next sections).…”

Section: Patterns In the Contact Maps Reveal Loops And Branchesmentioning

confidence: 96%

On the tree-like structure of rings in dense solutions

Michieletto

2016

Soft Matter

View full text Add to dashboard Cite

One of the most challenging problems in polymer physics is providing a theoretical description for the behaviour of rings in dense solutions and melts. Although it is nowadays well established that the overall size of a ring in these conditions scales like that of a collapsed globule, there is compelling evidence that rings may exhibit ramified and tree-like conformations. In this work I show how to characterise these local tree-like structures by measuring the local writhing of the rings' segments and by identifying the patterns of intra-chain contacts. These quantities reveal two major topological structures: loops and terminal branches which strongly suggest that the strictly double-folded "lattice animal" picture for rings in the melt may be replaced by a more relaxed tree-like structure accommodating loops. In particular, I show that one can identify hierarchically looped structures whose degree increases linearly with the size of a ring, and that terminal branches are found to store about 30% of the whole ring mass, irrespectively of its length. Finally, I draw an analogy between rings in the melt and slip-linked chains, where contact points are enforced by mobile slip-links and for which a field-theoretic treatment can be employed to get some insight into their typical conformations. These findings are ultimately discussed in the light of recent works on the static structure of rings and on the existence of inter-ring threadings.

show abstract

Compaction and segregation of sister chromatids via active loop extrusion

Cited by 280 publications

References 65 publications

A pathway for mitotic chromosome formation

A pathway for mitotic chromosome formation

SMC complexes differentially compact mitotic chromosomes according to genomic context

On the tree-like structure of rings in dense solutions

Contact Info

Product

Resources

About