Compaction and segregation of sister chromatids via active loop extrusion

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

doi:10.1101/038281

Cited by 106 publications

(183 citation statements)

References 58 publications

(95 reference statements)

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“…It is indeed becoming increasingly clear that ATP-driven processes are crucial to regulate chromatin organisation [84,85]; nonetheless how this is achieved remains largely obscure [86]. The work presented here provides a concrete example of how this may occur, and suggests that it would be of interest to develop experimental strategies to perturb, for instance, the interaction between reading and writing machines (e.g., by targeting the recruitment between Set1/2 and RNA polymerase, or between EZH2 and PRC, etc.…”

Section: Discussionmentioning

confidence: 99%

A Polymer Model with Epigenetic Recolouring Reveals a Pathway for thede novoEstablishment and 3D organisation of Chromatin Domains

Michieletto

Orlandini²,

Marenduzzo

2016

Preprint

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One of the most important problems in development is how epigenetic domains can be first established, and then maintained, within cells. To address this question, we propose a framework which couples 3D chromatin folding dynamics, to a "recolouring" process modeling the writing of epigenetic marks. Because many intra-chromatin interactions are mediated by bridging proteins, we consider a "two-state" model with self-attractive interactions between two epigenetic marks which are alike (either active or inactive). This model displays a first-order-like transition between a swollen, epigenetically disordered, phase, and a compact, epigenetically coherent, chromatin globule. If the self-attraction strength exceeds a threshold, the chromatin dynamics becomes glassy, and the corresponding interaction network freezes. By modifying the epigenetic read-write process according to more biologically-inspired assumptions, our polymer model with recolouring recapitulates the ultrasensitive response of epigenetic switches to perturbations, and accounts for long-lived multi-domain conformations, strikingly similar to the topologically-associating-domains observed in eukaryotic chromosomes.

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Section: Discussionmentioning

confidence: 99%

A Polymer Model with Epigenetic Recolouring Reveals a Pathway for thede novoEstablishment and 3D organisation of Chromatin Domains

Michieletto

Orlandini²,

Marenduzzo

2016

Preprint

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“…Polymer connectivity, stiffness, and excluded volume were implemented as previously described 14 . Extruded loops held by LEFs were implemented by connecting the two monomers held by the two heads of each LEF with a harmonic bond, as previously 14,61 .…”

Section: On-line Methodsmentioning

confidence: 99%

Two independent modes of chromatin organization revealed by cohesin removal

Schwarzer

Abdennur

Goloborodko

et al. 2017

Nature

Self Cite

1,025

114

1,115

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Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-large active and inactive compartments, and partitioning into sub-megabase domains (TADs). Yet, it remains unclear how these layers of organization form, interact with one another and impact genome functions. Here, we show that deletion of the cohesin-loading factor Nipbl, in mouse liver, leads to a dramatic reorganization of chromosomal folding. TADs and associated peaks vanish globally, even in the absence of transcriptional changes. In contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the 3D organization of the genome results from the interplay of two independent mechanisms: 1) cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; 2) cohesin-dependent formation of TADs, possibly by loop extrusion, which contributes to guide distant enhancers to their target genes.

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“…Two, non-mutually exclusive models have been proposed: cohesin stochastically tethers different DNA segments on the same chromosome (stochastic pairwise interactions) or the ring generates a chromatin loop by extruding a chromatin fiber via a passive or active mechanism (loop extrusions) [76,77]. Cohesin often establishes chromatin loops between enhancers and promoters [8].…”

Section: Intrachromosomal Interactions: Another Open Questionmentioning

confidence: 99%

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

Murayama

2018

Nucleus

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Cohesin is a ring-shaped, multi-subunit ATPase assembly that is fundamental to the spatiotemporal organization of chromosomes. The ring establishes a variety of chromosomal structures including sister chromatid cohesion and chromatin loops. At the core of the ring is a pair of highly conserved SMC (Structural Maintenance of Chromosomes) proteins, which are closed by the flexible kleisin subunit. In common with other essential SMC complexes including condensin and the SMC5-6 complex, cohesin encircles DNA inside its cavity, with the aid of HEAT (Huntingtin, elongation factor 3, protein phosphatase 2A and TOR) repeat auxiliary proteins. Through this topological embrace, cohesin is thought to establish a series of intra- and interchromosomal interactions by tethering more than one DNA molecule. Recent progress in biochemical reconstitution of cohesin provides molecular insights into how this ring complex topologically binds and mediates DNA-DNA interactions. Here, I review these studies and discuss how cohesin mediates such chromosome interactions.

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Compaction and segregation of sister chromatids via active loop extrusion

Cited by 106 publications

References 58 publications

A Polymer Model with Epigenetic Recolouring Reveals a Pathway for thede novoEstablishment and 3D organisation of Chromatin Domains

A Polymer Model with Epigenetic Recolouring Reveals a Pathway for thede novoEstablishment and 3D organisation of Chromatin Domains

Two independent modes of chromatin organization revealed by cohesin removal

DNA entry, exit and second DNA capture by cohesin: insights from biochemical experiments

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