Models that include supercoiling of topological domains reproduce several known features of interphase chromosomes

Benedetti, Fabrizio; Dorier, Julien; Burnier, Yannis; Stasiak, Andrzej

doi:10.1093/nar/gkt1353

Cited by 111 publications

(119 citation statements)

References 38 publications

(89 reference statements)

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“…In our model, we show that TADs emerge without requiring such specific interactions; any two regions of sticky monomers separated by a nonsticky linker would form TADs. Another study proposed that transcription-induced supercoiling may be responsible for the formation of TADs (Benedetti et al 2014). Although this model is consistent with our observation that sites of active transcription demarcate TAD boundaries, there is limited evidence that supercoiling of chromatinized DNA exists in Drosophila and other organisms.…”

Section: Discussionsupporting

confidence: 91%

Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains

et al. 2015

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Recent advances enabled by the Hi-C technique have unraveled many principles of chromosomal folding that were subsequently linked to disease and gene regulation. In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. Mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principles of TAD folding in Drosophila melanogaster, we performed Hi-C and poly(A) + RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e., the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predicts TAD boundaries much worse than active chromatin marks do. Interestingly, inter-TADs correspond to decompacted inter-bands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin. We propose the mechanism of TAD self-assembly based on the ability of nucleosomes from inactive chromatin to aggregate, and lack of this ability in acetylated nucleosomal arrays. Finally, we test this hypothesis by polymer simulations and find that TAD partitioning may be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin.

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Section: Discussionsupporting

confidence: 91%

Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains

et al. 2015

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“…These matrices are broadly used in biophysical experiments to determine the 3D organisation of genetic material of eukaryotes [34][35][36][37][38] and bacteria 4,39 . As in the case presented here, although on a much more complex level, characteristic patterns seem to emerge 35 , and their understanding is one of the major challenges in the field of biophysics.…”

Section: Patterns In the Contact Maps Reveal Loops And Branchesmentioning

confidence: 99%

On the tree-like structure of rings in dense solutions

Michieletto

2016

Soft Matter

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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.

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“…By using dynamic simulations, it was shown that including supercoiling into models of topological domain organization can qualitatively and quantitatively reproduce experimental 3C data obtained in eukaryotic cells. 93 Another work points to supercoiling and transcriptional activity as critical determinants of domain formation in bacteria. It was revealed that bacterial genome is composed of regions with increased frequency of contacts, highly reminiscent of topological domains in eukaryotic chromosomes.…”

Section: Dna Topology and Genome Architecturementioning

confidence: 99%

DNA topology and transcription

Kouzine¹,

Levens²,

Baranello³

2014

Nucleus

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Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions.

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Models that include supercoiling of topological domains reproduce several known features of interphase chromosomes

Cited by 111 publications

References 38 publications

Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains

Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains

On the tree-like structure of rings in dense solutions

DNA topology and transcription

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