Network models of chromatin structure

Pancaldi, Véra

doi:10.1016/j.gde.2023.102051

Cited by 9 publications

(2 citation statements)

References 68 publications

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“…Assortativity measures the preference for the nodes of a network to interact with other nodes that have the same characteristics. In ChAs analysis, a chromatin interaction network is built from a genome-wide contact map 28 . This network represents the genomic loci (nodes) displaying high frequency interactions amongst each other (Fig.…”

Section: Resultsmentioning

confidence: 99%

3D chromatin interactions involving Drosophila insulators are infrequent but preferential and arise before TADs and transcription

Messina,

Raynal,

Gurgo

et al. 2023

Nat Commun

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In mammals, insulators contribute to the regulation of loop extrusion to organize chromatin into topologically associating domains. In Drosophila the role of insulators in 3D genome organization is, however, under current debate. Here, we addressed this question by combining bioinformatics analysis and multiplexed chromatin imaging. We describe a class of Drosophila insulators enriched at regions forming preferential chromatin interactions genome-wide. Notably, most of these 3D interactions do not involve TAD borders. Multiplexed imaging shows that these interactions occur infrequently, and only rarely involve multiple genomic regions coalescing together in space in single cells. Finally, we show that non-border preferential 3D interactions enriched in this class of insulators are present before TADs and transcription during Drosophila development. Our results are inconsistent with insulators forming stable hubs in single cells, and instead suggest that they fine-tune existing 3D chromatin interactions, providing an additional regulatory layer for transcriptional regulation.

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Section: Resultsmentioning

confidence: 99%

3D chromatin interactions involving Drosophila insulators are infrequent but preferential and arise before TADs and transcription

Messina,

Raynal,

Gurgo

et al. 2023

Nat Commun

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“…Chromatin can be represented as a graph in which nodes are chromatin fragments and edges are experimentally detected contacts between fragments (through either sequencing based chromosome capture or any other 3D epigenome reconstruction technique). In this framework, TADs appear as modules in the network and chromatin interactions can be studied with network theory tools, to extract their statistical properties (Pancaldi, 2023).…”

Section: Introductionmentioning

confidence: 99%

Global chromatin reorganization and regulation of genes with specific evolutionary ages during differentiation and cancer

Raynal,

Sengupta,

Plewczynski

et al. 2023

Preprint

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The availability of unprecedented datasets detailing the organization of chromatin across species, developmental stages, cell types and diseases invites an integrated analysis of genome organization in three dimensions and its biological significance.In this study we attempt to formalize a hypothesis according to which the topological properties of the chromatin network can impact phenotypes, such as plasticity and variability. Our observations lead us to reconsider the theory according to which cancer cells re-acquire pluripotency through a reactivation of early evolutionary programs characteristic of species lacking complex body plans or even multicellularity.Recent work investigating gene variability across tissues and individuals in multiple species has shown that promoter sequence characteristics can be predictive of gene expression variability. Exploiting this dataset and others, we show that genes with specific promoter features and associated similar values of expression variability tend to have specific epigenomic marks and form preferential interactions in 3D, as quantified by chromatin assortativity. We then investigate whether rearrangements of the 3D topology of the chromatin network in differentiation and oncogenesis can change these associations between gene regulation and evolutionary age. We observed that evolutionary older genes, also broadly corresponding to the least variable genes, are strongly clustered in the chromatin network.We characterize the topology of promoter-centered chromatin networks as well as assortativities of gene ages and expression variability in multiple datasets capturing topological changes in differentiation (embryonic stem cells, B cells) and find some of these changes to be reversed during oncogenesis.

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