Polymer Model Integrates Imaging and Epigenomics to Elucidate the Role of the Cell’s Microenvironment in Shaping 4D Chromatin Organization
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE275755 | GEO | 2025/03/18
REPOSITORIES: GEO
Similar Datasets
Project description:Chromatin epigenetic markers have been recognized to colocalize with phase-separated genomic compartments. While the correlation between 3D organization and epigenetic changes in response to extracellular stimuli has been observed, the causal physical underpinnings of 4D chromatin reorganization with changes in the cell microenvironment remain elusive. To tackle this, we introduce a dynamic, histone epigenetic remodeler-driven polymer model that incorporates next-generation sequencing data to identify active and repressed chromatin regions. The proposed chromatin-chromatin interaction energetics and diffusion-epigenetic reaction driven dynamics predict the formation and maintenance of characteristic heterochromatin-rich domains. We establish a scaling relation for the sizes of these chromatin domains with modulation of epigenetic reaction rates. Additionally, our model predicts that the epigenetic and accessibility changes occur predominantly at the domain boundaries resulting from the diffusion-reaction balance. These predictions are verified using super-resolution imaging and Hi-C sequencing of hyperacetylated melanoma cells. Subsequent RNA-seq analysis suggests a pivotal role of these epigenetic shifts in driving the cell’s phenotype. Extending our model’s universality, we validate our mesoscale findings against chromatin rearrangement resulting from changes in the microenvironmental substrate stiffness. Lastly, we evaluate the effect of altering the epigenetic reaction rates in silico and uncover a domain boundary driven cell-type invariant mechanism by which chromatin organization can drive epigenetic memory formation. These findings significantly advance our comprehension of how chromatin dynamics impact both short-term (immediate response) and long-term (memory) cellular behavior.
2025-03-18 | GSE275745 | GEO
Project description:Chromatin epigenetic markers have been recognized to colocalize with phase-separated genomic compartments. While the correlation between 3D organization and epigenetic changes in response to extracellular stimuli has been observed, the causal physical underpinnings of 4D chromatin reorganization with changes in the cell microenvironment remain elusive. To tackle this, we introduce a dynamic, histone epigenetic remodeler-driven polymer model that incorporates next-generation sequencing data to identify active and repressed chromatin regions. The proposed chromatin-chromatin interaction energetics and diffusion-epigenetic reaction driven dynamics predict the formation and maintenance of characteristic heterochromatin-rich domains. We establish a scaling relation for the sizes of these chromatin domains with modulation of epigenetic reaction rates. Additionally, our model predicts that the epigenetic and accessibility changes occur predominantly at the domain boundaries resulting from the diffusion-reaction balance. These predictions are verified using super-resolution imaging and Hi-C sequencing of hyperacetylated melanoma cells. Subsequent RNA-seq analysis suggests a pivotal role of these epigenetic shifts in driving the cell’s phenotype. Extending our model’s universality, we validate our mesoscale findings against chromatin rearrangement resulting from changes in the microenvironmental substrate stiffness. Lastly, we evaluate the effect of altering the epigenetic reaction rates in silico and uncover a domain boundary driven cell-type invariant mechanism by which chromatin organization can drive epigenetic memory formation. These findings significantly advance our comprehension of how chromatin dynamics impact both short-term (immediate response) and long-term (memory) cellular behavior.
2025-03-18 | GSE275744 | GEO
Project description:Polymer Model Integrates Imaging and Epigenomics to Elucidate the Role of the Cell’s Microenvironment in Shaping 4D Chromatin Organization
| PRJNA1152908 | ENA
Project description:Polymer Model Integrates Imaging and Epigenomics to Elucidate the Role of the Cell’s Microenvironment in Shaping 4D Chromatin Organization [Hi-C]
| PRJNA1152895 | ENA
Project description:Polymer Model Integrates Imaging and Epigenomics to Elucidate the Role of the Cell’s Microenvironment in Shaping 4D Chromatin Organization [RNA-Seq]
| PRJNA1152894 | ENA
Project description:Extending across multiple length scales, dynamic chromatin structure is linked to transcription through the regulation of genome organization. However, no individual technique can fully elucidate this structure and its relation to molecular function at all length and time scales at both a single-cell level and a population level. Here, we present a multitechnique nanoscale chromatin imaging and analysis (nano-ChIA) platform that consolidates electron tomography of the primary chromatin fiber, optical super-resolution imaging of transcription processes, and label-free nano-sensing of chromatin packing and its dynamics in live cells. Using nano-ChIA, we observed that chromatin is localized into spatially separable packing domains, with an average diameter of around 200 nanometers, sub-megabase genomic size, and an internal fractal structure. The chromatin packing behavior of these domains exhibits a complex bidirectional relationship with active gene transcription. Furthermore, we found that properties of PDs are correlated among progenitor and progeny cells across cell division.
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Project description:The resolution of chromatin conformation capture technologies keeps increasing, and the recent nucleosome resolution chromatin contact maps allow us to explore how fine-scale 3D chromatin organization is related to epigenomic states in human cells. Using publicly available Micro-C datasets, we develop a deep learning model, CAESAR, to learn a mapping function from epigenomic features to 3D chromatin organization. The model accurately predicts fine-scale structures, such as short-range chromatin loops and stripes, that Hi-C fails to detect. With existing epigenomic datasets from ENCODE and Roadmap Epigenomics Project, we successfully impute high-resolution 3D chromatin contact maps for 91 human tissues and cell lines. In the imputed high-resolution contact maps, we identify the spatial interactions between genes and their experimentally validated regulatory elements, demonstrating CAESAR's potential in coupling transcriptional regulation with 3D chromatin organization at high resolution.
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Project description:The 4D organization of the interphase nucleus, or the 4D Nucleome (4DN), reflects a dynamical interaction between 3D genome structure and function and its relationship to phenotype. We present initial analyses of the human 4DN, capturing genome-wide structure using chromosome conformation capture and 3D imaging, and function using RNA-sequencing. We introduce a quantitative index that measures underlying topological stability of a genomic region. Our results show that structural features of genomic regions correlate with function with surprising persistence over time. Furthermore, constructing genome-wide gene-level contact maps aided in identifying gene pairs with high potential for coregulation and colocalization in a manner consistent with expression via transcription factories. We additionally use 2D phase planes to visualize patterns in 4DN data. Finally, we evaluated gene pairs within a circadian gene module using 3D imaging, and found periodicity in the movement of clock circadian regulator and period circadian clock 2 relative to each other that followed a circadian rhythm and entrained with their expression.
| S-EPMC4491792 | biostudies-literature
Project description:The 3D genome is characterized by a complex organization made of genomic and epigenomic layers with profound implications on gene regulation and cell function. However, the understanding of the fundamental mechanisms driving the crosstalk between nuclear architecture and (epi)genomic information is still lacking. The plant Arabidopsis thaliana is a powerful model organism to address these questions owing to its compact genome for which we have a rich collection of microscopy, chromosome conformation capture (Hi-C) and ChIP-seq experiments. Using polymer modelling, we investigate the roles of nucleolus formation and epigenomics-driven interactions in shaping the 3D genome of A. thaliana. By validation of several predictions with published data, we demonstrate that self-attracting nucleolar organizing regions and repulsive constitutive heterochromatin are major mechanisms to regulate the organization of chromosomes. Simulations also suggest that interphase chromosomes maintain a partial structural memory of the V-shapes, typical of (sub)metacentric chromosomes in anaphase. Additionally, self-attraction between facultative heterochromatin regions facilitates the formation of Polycomb bodies hosting H3K27me3-enriched gene-clusters. Since nucleolus and heterochromatin are highly-conserved in eukaryotic cells, our findings pave the way for a comprehensive characterization of the generic principles that are likely to shape and regulate the 3D genome in many species.
| S-EPMC7913674 | biostudies-literature
Project description:BackgroundThe processes of gene transcription, translation, as well as the reactions taking place between gene products, are subject to stochastic fluctuations. These stochastic events are being increasingly examined as it emerges that they can be crucial in the cell's survival. In a previous study we had examined the transcription patterns of two bacterial species (Escherichia coli and Bacillus subtilis) to elucidate the nucleoid's organization. The basic idea is that genes that share transcription patterns, must share some sort of spatial relationship, even if they are not close to each other on the chromosome. We had found that picking any gene at random, its transcription will be correlated with genes at well-defined short - as well as long-range distances, leaving the explanation of the latter an open question. In this paper we study the transcription correlations when the only transcription taking place is stochastic, in other words, no active or "deterministic" transcription takes place. To this purpose we use transcription data of Sinorhizobium meliloti.ResultsEven when only stochastic transcription takes place, the co-expression of genes varies as a function of the distance between genes: we observe again the short-range as well as the regular, long-range correlation patterns.ConclusionWe explain these latter with a model based on the physical constraints acting on the DNA, forcing it into a conformation of groups of a few successive large and transcribed loops, which are evenly spaced along the chromosome and separated by small, non-transcribed loops. We discuss the question about the link between shared transcription patterns and physiological relationship and come to the conclusion that when genes are distantly placed along the chromosome, the transcription correlation does not imply a physiological relationship.
| S-EPMC2270832 | biostudies-literature