ArticleProceedings of the National Academy of Sciences of the United States of America2021
Four-dimensional chromosome reconstruction elucidates the spatiotemporal reorganization of the mammalian X chromosome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- A continuum-based reaction-diffusion model for spread of gene silencing in chromosomal inactivation.RNA (New York, N.Y.) · 2026Article
- Deep learning enabled prediction of nuclear lamina-associated chromatin.Patterns (New York, N.Y.) · 2026Article
- Article
- Endocrine therapy-specific lineage and partial epithelial-mesenchymal reprogramming defines divergent resistant cell-states in ER+ breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Multiscale chromatin modeling of chromosome X structural changes upon inactivation highlights the differential regulatory mechanism ofbioRxiv : the preprint server for biology · 2026Article
- From 2D to 4D: a containerized workflow and browser to explore dynamic chromatin architecture.BMC bioinformatics · 2026Article
- Jpx RNA controls Xist induction through spatial reorganization of the mouse X-inactivation center.Developmental cell · 2025Article
- XIST Loss Induces Variable Transcriptional Responses Dependent on Cell States.Non-coding RNA · 2025Article
- An evolving landscape of PRC2-RNA interactions in chromatin regulation.Nature reviews. Molecular cell biology · 2025Review
- From 2D to 4D: a Containerized Workflow and Browser to Explore Dynamic Chromatin Architecture.bioRxiv : the preprint server for biology · 2025Article
- Predicting gene expression changes from chromatin structure modification.NPJ systems biology and applications · 2025Article
- Article
- Widespread 3D genome reorganization precedes programmed DNA rearrangement inbioRxiv : the preprint server for biology · 2025Article
- Advancements and future directions in single-cell Hi-C based 3D chromatin modeling.Computational and structural biotechnology journal · 2024Review
- Supercomputing in the biological sciences: Toward Zettascale and Yottascale simulations.Current opinion in structural biology · 2024Review
- Genome structural dynamics: insights from Gaussian network analysis of Hi-C data.Briefings in functional genomics · 2024Article
- Article
- A critical role for X-chromosome architecture in mammalian X-chromosome dosage compensation.Current opinion in genetics & development · 2024Review
- Embracing exascale computing in nucleic acid simulations.Current opinion in structural biology · 2024Review
- Multi-omics analysis reveals the dynamic interplay between Vero host chromatin structure and function during vaccinia virus infection.Communications biology · 2024Article
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7 authors.
Funding
Abstract
Chromosomes are segmented into domains and compartments, but how these structures are spatially related in three dimensions (3D) is unclear. Here, we developed tools that directly extract 3D information from Hi-C experiments and integrate the data across time. With our "4DHiC" method, we use X chromosome inactivation (XCI) as a model to examine the time evolution of 3D chromosome architecture during large-scale changes in gene expression. Our modeling resulted in several insights. Both A/B and S1/S2 compartments divide the X chromosome into hemisphere-like structures suggestive of a spatial phase-separation. During the XCI, the X chromosome transits through A/B, S1/S2, and megadomain structures by undergoing only partial mixing to assume new structures. Interestingly, when an active X chromosome (Xa) is reorganized into an inactive X chromosome (Xi), original underlying compartment structures are not fully eliminated within the Xi superstructure. Our study affirms slow mixing dynamics in the inner chromosome core and faster dynamics near the surface where escapees reside. Once established, the Xa and Xi resemble glassy polymers where mixing no longer occurs. Finally, Xist RNA molecules initially reside within the A compartment but transition to the interface between the A and B hemispheres and then spread between hemispheres via both surface and core to establish the Xi.
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