Polymer model integrates imaging and sequencing to reveal how nanoscale heterochromatin domains influence gene expression DOI Creative Commons

Vinayak Vinayak,

Ramin Basir, Rosela Golloshi

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 23, 2025

Abstract Chromatin organization regulates gene expression, with nanoscale heterochromatin domains playing a fundamental role. Their size varies microenvironmental stiffness and epigenetic interventions, but how these factors regulate their formation influence transcription remains unclear. To address this, we developed sequencing-informed copolymer model that simulates chromatin evolution through diffusion active reactions. Our predicts the of quantifies domain scales reaction rates, showing compaction changes primarily occur at boundaries. We validated predictions via Hi-C super-resolution imaging hyperacetylated melanoma cells identified differential expression metastasis-related genes RNA-seq. our findings in hMSCs, where rates respond to stiffness. Conclusively, simulations reveal boundaries memory. These demonstrate external cues drive transcriptional memory development disease.

Language: Английский

Chromatin domains in the cell: Phase separation and condensation DOI
Shin Fujishiro, Masaki Sasai, Kazuhiro Maeshima

et al.

Current Opinion in Structural Biology, Journal Year: 2025, Volume and Issue: 91, P. 103006 - 103006

Published: Feb. 20, 2025

Language: Английский

Citations

0
Three-color single-molecule localization microscopy in chromatin DOI Creative Commons
Nicolas Acosta, Ruyi Gong, Yuanzhe Su

et al.

Light Science & Applications, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 17, 2025

Abstract Super-resolution microscopy has revolutionized our ability to visualize structures below the diffraction limit of conventional optical and is particularly useful for investigating complex biological targets like chromatin. Chromatin exhibits a hierarchical organization with structural compartments domains at different length scales, from nanometers micrometers. Single molecule localization (SMLM) methods, such as STORM, are essential studying chromatin supra-nucleosome level due their target epigenetic marks that determine organization. Multi-label imaging necessary unpack its complexity. However, these efforts challenged by high-density nuclear environment, which can affect antibody binding affinities, diffusivity non-specific interactions. Optimizing buffer conditions, fluorophore stability, specificity crucial achieving effective conjugates. Here, we demonstrate sequential immunolabeling protocol reliably enables three-color studies within dense environment. This couples multiplexed datasets robust analysis algorithm, utilizes localizations one seed points distance, density multi-label joint affinity measurements explore all three targets. Applying this algorithm analyze distance reveals heterochromatin euchromatin not-distinct territories, but transcription couple periphery heterochromatic clusters. work step in molecular environment capacity investigation multi-component systems enhanced accuracy.

Language: Английский

Citations

0
Polymer model integrates imaging and sequencing to reveal how nanoscale heterochromatin domains influence gene expression DOI Creative Commons

Vinayak Vinayak,

Ramin Basir, Rosela Golloshi

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 23, 2025

Abstract Chromatin organization regulates gene expression, with nanoscale heterochromatin domains playing a fundamental role. Their size varies microenvironmental stiffness and epigenetic interventions, but how these factors regulate their formation influence transcription remains unclear. To address this, we developed sequencing-informed copolymer model that simulates chromatin evolution through diffusion active reactions. Our predicts the of quantifies domain scales reaction rates, showing compaction changes primarily occur at boundaries. We validated predictions via Hi-C super-resolution imaging hyperacetylated melanoma cells identified differential expression metastasis-related genes RNA-seq. our findings in hMSCs, where rates respond to stiffness. Conclusively, simulations reveal boundaries memory. These demonstrate external cues drive transcriptional memory development disease.

Language: Английский

Citations

0