4D epigenomics: deciphering the coupling between genome folding and epigenomic regulation with biophysical modeling

Abdulla, Amith Z.; Salari, Hossein; Tortora, Maxime M. C.; Vaillant, Cédric; Jost, Daniel

doi:10.1016/j.gde.2023.102033

Cited by 12 publications

(8 citation statements)

References 94 publications

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“…In the recent years, polymer physics has provided concrete frameworks to characterize and rationalize the mechanisms driving the spatiotemporal dynamics of chromosomes: from SMC-mediated loop extrusion for TAD formation , to epigenomic–driven interactions for chromatin 3D compartmentalization. , With recent experimental advances, such as Micro-C , or chromosome tracing, , it may be now possible to study a specific locus at near-nucleosome resolution (200 bp–1 kbp) with good statistics. Hence, more detailed polymer models are required to finely study the organization of specific regions of interest and the interplay between the various physicochemical mechanisms that may act locally …”

Section: Introductionmentioning

confidence: 99%

Topological Constraints and Finite-Size Effects in Quantitative Polymer Models of Chromatin Organization

Abdulla,

Tortora,

Vaillant

et al. 2023

Macromolecules

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Polymer physics simulations have provided a versatile framework to quantitatively explore the complex mechanisms driving chromosome organization. However, simulating whole chromosomes over biologically relevant time scales at a high resolution often constitutes a computationally intensive task, while genes or other regions of biological interest may typically only span a small fraction of the full chromosome length. Conversely, only simulating the subchromosomal region of interest might provide an oversimplistic or even wrong description of the mechanism controlling the 3D organization. In this work, we characterize what should be the minimal length of the chromosome to be simulated in order to correctly capture the properties of a given restricted region. In particular, since the physics of long, topologically constrained polymers may significantly deviate from those of shorter chains, we theoretically investigate how chromosomes being a long polymer quantitatively affects the structure and dynamics of their subsegments. We show that increasing the total polymer length impacts on the topological constraints acting on the system and thus influences the compaction and mobility of subchains. Depending on the entanglement properties of the system, we derive a phenomenological relation defining the minimal total length to account for to maintain a correct topological regime. We finally detail the implications of these conclusions in the case of several biological systems.

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Section: Introductionmentioning

confidence: 99%

Topological Constraints and Finite-Size Effects in Quantitative Polymer Models of Chromatin Organization

Abdulla,

Tortora,

Vaillant

et al. 2023

Macromolecules

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“…Given the clear compartmental pattern observed in Hi-C, we first sought to explain the unique behavior of S compartment by modeling affinity-mediated compartmentalization of chromosomes, which has successfully recapitulated compartmentalization in a variety of other organisms 43,44 .…”

Section: Phenomenological Model Reveals Principles Of A/b/s Compartme...mentioning

confidence: 99%

Unique territorial and compartmental organization of chromosomes in the holocentric silkmoth

Gil,

Navarrete,

Rosin

et al. 2023

Preprint

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The hallmarks of chromosome organization in multicellular eukaryotes are chromosome territories (CT), chromatin compartments, and different types of domains, including topologically associated domains (TADs). Yet, most of these concepts derive from analyses of organisms with monocentric chromosomes. Here we describe the 3D genome architecture of an organism with holocentric chromosomes, the silkwormBombyx mori. At the genome-wide scale,B. morichromosomes form highly separated territories and lack substantial trans contacts. As described in other eukaryotes,B. morichromosomes segregate into an active A and an inactive B compartment. Remarkably, we also identify a third compartment, Secluded »S», with a unique contact pattern. Compartment S shows strong enrichment of short-range contacts and depletion of long-range contacts. It hosts a unique combination of genetic and epigenetic features, localizes at the periphery of CTs and shows developmental plasticity. Biophysical modeling shows that formation of such secluded domains requires a new mechanism – a high density of extruded loops within them along with low level of extrusion and compartmentalization of A and B. Together with other evidence of loop extrusion in interphase, this suggests SMC-mediated loop extrusion in this insect. Overall, our analyses highlight the evolutionary plasticity of 3D genome organization driven by a new combination of known processes.

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“…The initiation and sustained maintenance of the epigenetic state are theorized to depend on the recruitment of histone- modifying enzymes (HMEs) to specific genomic states ( 96 - 98 ). Such recruitment is facilitated either through collaborations with DNA-binding proteins or via RNA interference (RNAi) pathways ( 99 ). Some models integrate sequence-specific nucleation and its interaction with the reader-writer process within a 3D context ( 100 ).…”

Section: Molecular Mechanisms Underlying the Interplay Between Chroma...mentioning

confidence: 99%

Interplay between epigenome and 3D chromatin structure

Han,

Issagulova,

Park

2023

BMB Rep

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Epigenetic mechanisms, primarily mediated through histone and DNA modifications, play a pivotal role in orchestrating the functional identity of a cell and its response to environmental cues. Similarly, the spatial arrangement of chromatin within the three- dimensional (3D) nucleus has been recognized as a significant factor influencing genomic function. Investigating the relationship between epigenetic regulation and 3D chromatin structure has revealed correlation and causality between these processes, from the global alignment of average chromatin structure with chromatin marks to the nuanced correlations at smaller scales. This review aims to dissect the biological significance and the interplay between the epigenome and 3D chromatin structure, while also exploring the underlying molecular mechanisms. By synthesizing insights from both experimental and modeling perspectives, we seek to provide a comprehensive understanding of cellular functions.

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4D epigenomics: deciphering the coupling between genome folding and epigenomic regulation with biophysical modeling

Cited by 12 publications

References 94 publications

Topological Constraints and Finite-Size Effects in Quantitative Polymer Models of Chromatin Organization

Topological Constraints and Finite-Size Effects in Quantitative Polymer Models of Chromatin Organization

Unique territorial and compartmental organization of chromosomes in the holocentric silkmoth

Interplay between epigenome and 3D chromatin structure

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