Four-dimensional chromosome reconstruction elucidates the spatiotemporal reorganization of the mammalian X chromosome
Abstract
Significance Breakthrough technological advances such as Hi-C have enabled large-scale sequencing of pairwise genomic contacts. However, translating the 2D contacts to 3D spatial models remains challenging. Here we develop the “4DHiC” modeling method to infer 3D information from 2D datasets across time and construct a 3D model of the inactive X-chromosome (Xi). Our model not only demonstrates a spatial phase-separation between A/B and S1/S2 compartments to form “hemispheres,” but also reveals persistent smaller-scale structures hidden under the Xi superstructure. We also simulate Xist RNA spreading dynamics and deduce that the RNA spreads between hemispheres via both surface and core to establish the Xi. Our 4DHiC will serve a growing demand for data-driven methodologies that extract spatial information from biochemical interaction data.
- Authors:
-
[1];
- Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545,, Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114,, Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA 02114,
- Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114,, Department of Genetics, The Blavatnik Institute, Harvard Medical School, Boston, MA 02114,
- Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545,
- Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545,, New Mexico Consortium, Los Alamos, NM 87545
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1825581
- Grant/Contract Number:
- 20210082DR; 20210134ER
- Resource Type:
- Published Article
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 118 Journal Issue: 42; Journal ID: ISSN 0027-8424
- Publisher:
- Proceedings of the National Academy of Sciences
- Country of Publication:
- United States
- Language:
- English
Citation Formats
Lappala, Anna, Wang, Chen-Yu, Kriz, Andrea, Michalk, Hunter, Tan, Kevin, Lee, Jeannie T., and Sanbonmatsu, Karissa Y. Four-dimensional chromosome reconstruction elucidates the spatiotemporal reorganization of the mammalian X chromosome. United States: N. p., 2021.
Web. doi:10.1073/pnas.2107092118.
Lappala, Anna, Wang, Chen-Yu, Kriz, Andrea, Michalk, Hunter, Tan, Kevin, Lee, Jeannie T., & Sanbonmatsu, Karissa Y. Four-dimensional chromosome reconstruction elucidates the spatiotemporal reorganization of the mammalian X chromosome. United States. https://doi.org/10.1073/pnas.2107092118
Lappala, Anna, Wang, Chen-Yu, Kriz, Andrea, Michalk, Hunter, Tan, Kevin, Lee, Jeannie T., and Sanbonmatsu, Karissa Y. Wed .
"Four-dimensional chromosome reconstruction elucidates the spatiotemporal reorganization of the mammalian X chromosome". United States. https://doi.org/10.1073/pnas.2107092118.
@article{osti_1825581,
title = {Four-dimensional chromosome reconstruction elucidates the spatiotemporal reorganization of the mammalian X chromosome},
author = {Lappala, Anna and Wang, Chen-Yu and Kriz, Andrea and Michalk, Hunter and Tan, Kevin and Lee, Jeannie T. and Sanbonmatsu, Karissa Y.},
abstractNote = {Significance Breakthrough technological advances such as Hi-C have enabled large-scale sequencing of pairwise genomic contacts. However, translating the 2D contacts to 3D spatial models remains challenging. Here we develop the “4DHiC” modeling method to infer 3D information from 2D datasets across time and construct a 3D model of the inactive X-chromosome (Xi). Our model not only demonstrates a spatial phase-separation between A/B and S1/S2 compartments to form “hemispheres,” but also reveals persistent smaller-scale structures hidden under the Xi superstructure. We also simulate Xist RNA spreading dynamics and deduce that the RNA spreads between hemispheres via both surface and core to establish the Xi. Our 4DHiC will serve a growing demand for data-driven methodologies that extract spatial information from biochemical interaction data.},
doi = {10.1073/pnas.2107092118},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 42,
volume = 118,
place = {United States},
year = {2021},
month = {10}
}
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1073/pnas.2107092118
https://doi.org/10.1073/pnas.2107092118
Other availability
Search WorldCat to find libraries that may hold this journal
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.
Works referenced in this record:
High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation
journal, October 2013
- Simon, Matthew D.; Pinter, Stefan F.; Fang, Rui
- Nature, Vol. 504, Issue 7480
Structure and Dynamics of Interphase Chromosomes
journal, August 2008
- Rosa, Angelo; Everaers, Ralf
- PLoS Computational Biology, Vol. 4, Issue 8
The mouse DXZ4 homolog retains Ctcf binding and proximity to Pls3 despite substantial organizational differences compared to the primate macrosatellite
journal, January 2012
- Horakova, Andrea H.; Calabrese, J. Mauro; McLaughlin, Christine R.
- Genome Biology, Vol. 13, Issue 8
Megadomains and superloops form dynamically but are dispensable for X-chromosome inactivation and gene escape
journal, November 2018
- Froberg, John E.; Pinter, Stefan F.; Kriz, Andrea J.
- Nature Communications, Vol. 9, Issue 1
CTCF Binding Polarity Determines Chromatin Looping
journal, November 2015
- de Wit, Elzo; Vos, Erica S. M.; Holwerda, Sjoerd J. B.
- Molecular Cell, Vol. 60, Issue 4
Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains
journal, August 2014
- Jost, Daniel; Carrivain, Pascal; Cavalli, Giacomo
- Nucleic Acids Research, Vol. 42, Issue 15
Structural organization of the inactive X chromosome in the mouse
journal, July 2016
- Giorgetti, Luca; Lajoie, Bryan R.; Carter, Ava C.
- Nature, Vol. 535, Issue 7613
Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization
journal, May 2017
- Nora, Elphège P.; Goloborodko, Anton; Valton, Anne-Laure
- Cell, Vol. 169, Issue 5
Physical and data structure of 3D genome
journal, January 2020
- Huang, Kai; Li, Yue; Shim, Anne R.
- Science Advances, Vol. 6, Issue 2
SMCHD1 Merges Chromosome Compartments and Assists Formation of Super-Structures on the Inactive X
journal, July 2018
- Wang, Chen-Yu; Jégu, Teddy; Chu, Hsueh-Ping
- Cell, Vol. 174, Issue 2
Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci
journal, April 2014
- Smeets, Daniel; Markaki, Yolanda; Schmid, Volker J.
- Epigenetics & Chromatin, Vol. 7, Issue 1
Transferable model for chromosome architecture
journal, September 2016
- Di Pierro, Michele; Zhang, Bin; Aiden, Erez Lieberman
- Proceedings of the National Academy of Sciences, Vol. 113, Issue 43
The X chromosome in space
journal, May 2017
- Jégu, Teddy; Aeby, Eric; Lee, Jeannie T.
- Nature Reviews Genetics, Vol. 18, Issue 6
An Overview of Genome Organization and How We Got There: from FISH to Hi-C
journal, September 2015
- Fraser, James; Williamson, Iain; Bickmore, Wendy A.
- Microbiology and Molecular Biology Reviews, Vol. 79, Issue 3
Fast Parallel Algorithms for Short-Range Molecular Dynamics
journal, March 1995
- Plimpton, Steve
- Journal of Computational Physics, Vol. 117, Issue 1
XIST RNA paints the inactive X chromosome at interphase: evidence for a novel RNA involved in nuclear/chromosome structure.
journal, February 1996
- Clemson, C. M.; McNeil, J. A.; Willard, H. F.
- Journal of Cell Biology, Vol. 132, Issue 3
Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture
journal, July 2016
- Darrow, Emily M.; Huntley, Miriam H.; Dudchenko, Olga
- Proceedings of the National Academy of Sciences, Vol. 113, Issue 31
Disruptions of Topological Chromatin Domains Cause Pathogenic Rewiring of Gene-Enhancer Interactions
journal, May 2015
- Lupiáñez, Darío G.; Kraft, Katerina; Heinrich, Verena
- Cell, Vol. 161, Issue 5
Bipartite structure of the inactive mouse X chromosome
journal, August 2015
- Deng, Xinxian; Ma, Wenxiu; Ramani, Vijay
- Genome Biology, Vol. 16, Issue 1
The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA
journal, June 2011
- Splinter, E.; de Wit, E.; Nora, E. P.
- Genes & Development, Vol. 25, Issue 13
The structure of histone-depleted metaphase chromosomes
journal, November 1977
- Paulson, James R.; Laemmli, U. K.
- Cell, Vol. 12, Issue 3
Spatial organization of chromatin domains and compartments in single chromosomes
journal, July 2016
- Wang, Siyuan; Su, Jun-Han; Beliveau, Brian J.
- Science, Vol. 353, Issue 6299
Mechanistic modeling of chromatin folding to understand function
journal, June 2020
- Brackey, Chris A.; Marenduzzo, Davide; Gilbert, Nick
- Nature Methods, Vol. 17, Issue 8
Comparison of the Hi-C, GAM and SPRITE methods using polymer models of chromatin
journal, May 2021
- Fiorillo, Luca; Musella, Francesco; Conte, Mattia
- Nature Methods, Vol. 18, Issue 5
Scaling molecular dynamics beyond 100,000 processor cores for large‐scale biophysical simulations
journal, April 2019
- Jung, Jaewoon; Nishima, Wataru; Daniels, Marcus
- Journal of Computational Chemistry, Vol. 40, Issue 21
“Raindrop” Coalescence of Polymer Chains during Coil–Globule Transition
journal, January 2013
- Lappala, Anna; Terentjev, Eugene M.
- Macromolecules, Vol. 46, Issue 3
Smchd1 regulates long-range chromatin interactions on the inactive X chromosome and at Hox clusters
journal, August 2018
- Jansz, Natasha; Keniry, Andrew; Trussart, Marie
- Nature Structural & Molecular Biology, Vol. 25, Issue 9
Topological domains in mammalian genomes identified by analysis of chromatin interactions
journal, April 2012
- Dixon, Jesse R.; Selvaraj, Siddarth; Yue, Feng
- Nature, Vol. 485, Issue 7398
Integrating Hi-C and FISH data for modeling of the 3D organization of chromosomes
journal, May 2019
- Abbas, Ahmed; He, Xuan; Niu, Jing
- Nature Communications, Vol. 10, Issue 1
Multiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome
journal, December 2004
- Chadwick, B. P.; Willard, H. F.
- Proceedings of the National Academy of Sciences, Vol. 101, Issue 50
Developmentally regulated Shh expression is robust to TAD perturbations
journal, January 2019
- Williamson, Iain; Kane, Lauren; Devenney, Paul S.
- Development
Automatic analysis and 3D-modelling of Hi-C data using TADbit reveals structural features of the fly chromatin colors
journal, July 2017
- Serra, François; Baù, Davide; Goodstadt, Mike
- PLOS Computational Biology, Vol. 13, Issue 7
ReaDDy 2: Fast and flexible software framework for interacting-particle reaction dynamics
journal, February 2019
- Hoffmann, Moritz; Fröhner, Christoph; Noé, Frank
- PLOS Computational Biology, Vol. 15, Issue 2
Dynamics of gene silencing during X inactivation using allele-specific RNA-seq
journal, August 2015
- Marks, Hendrik; Kerstens, Hindrik H. D.; Barakat, Tahsin Stefan
- Genome Biology, Vol. 16, Issue 1
Compaction and segregation of sister chromatids via active loop extrusion
journal, May 2016
- Goloborodko, Anton; Imakaev, Maxim V.; Marko, John F.
- eLife, Vol. 5
The Cohesin Release Factor WAPL Restricts Chromatin Loop Extension
journal, May 2017
- Haarhuis, Judith H. I.; van der Weide, Robin H.; Blomen, Vincent A.
- Cell, Vol. 169, Issue 4
Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
journal, October 2009
- Lieberman-Aiden, E.; van Berkum, N. L.; Williams, L.
- Science, Vol. 326, Issue 5950
A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation
journal, July 2015
- Minajigi, Anand; Froberg, John E.; Wei, Chunyao
- Science, Vol. 349, Issue 6245
Mesoscale Modeling Reveals Hierarchical Looping of Chromatin Fibers Near Gene Regulatory Elements
journal, May 2016
- Bascom, Gavin D.; Sanbonmatsu, Karissa Y.; Schlick, Tamar
- The Journal of Physical Chemistry B, Vol. 120, Issue 33
Chrom3D: three-dimensional genome modeling from Hi-C and nuclear lamin-genome contacts
journal, January 2017
- Paulsen, Jonas; Sekelja, Monika; Oldenburg, Anja R.
- Genome Biology, Vol. 18, Issue 1
A new model for random X chromosome inactivation
journal, January 2009
- Starmer, Joshua; Magnuson, Terry
- Development, Vol. 136, Issue 1
The X chromosome is organized into a gene-rich outer rim and an internal core containing silenced nongenic sequences
journal, May 2006
- Clemson, C. M.; Hall, L. L.; Byron, M.
- Proceedings of the National Academy of Sciences, Vol. 103, Issue 20
Balancing cohesin eviction and retention prevents aberrant chromosomal interactions, Polycomb-mediated repression, and X-inactivation
journal, May 2021
- Kriz, Andrea J.; Colognori, David; Sunwoo, Hongjae
- Molecular Cell, Vol. 81, Issue 9
The Xist lncRNA Exploits Three-Dimensional Genome Architecture to Spread Across the X Chromosome
journal, July 2013
- Engreitz, J. M.; Pandya-Jones, A.; McDonel, P.
- Science, Vol. 341, Issue 6147
A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced
journal, August 2006
- Chaumeil, J.
- Genes & Development, Vol. 20, Issue 16
Connectivity and free-surface effects in polymer glasses
journal, March 2019
- Lappala, Anna; Sefton, Luke; Fenimore, Paul W.
- Scientific Reports, Vol. 9, Issue 1
The non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalisation on the inactive X chromosome
journal, January 2019
- Gdula, Michal R.; Nesterova, Tatyana B.; Pintacuda, Greta
- Nature Communications, Vol. 10, Issue 1
CTCF and Cohesin in Genome Folding and Transcriptional Gene Regulation
journal, August 2016
- Merkenschlager, Matthias; Nora, Elphège P.
- Annual Review of Genomics and Human Genetics, Vol. 17, Issue 1
PRC1 collaborates with SMCHD1 to fold the X-chromosome and spread Xist RNA between chromosome compartments
journal, July 2019
- Wang, Chen-Yu; Colognori, David; Sunwoo, Hongjae
- Nature Communications, Vol. 10, Issue 1
Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene
journal, May 2000
- Bell, Adam C.; Felsenfeld, Gary
- Nature, Vol. 405, Issue 6785
Cohesin Loss Eliminates All Loop Domains
journal, October 2017
- Rao, Suhas S. P.; Huang, Su-Chen; Glenn St Hilaire, Brian
- Cell, Vol. 171, Issue 2
CRISPR Inversion of CTCF Sites Alters Genome Topology and Enhancer/Promoter Function
journal, August 2015
- Guo, Ya; Xu, Quan; Canzio, Daniele
- Cell, Vol. 162, Issue 4
LINE-1 Activity in Facultative Heterochromatin Formation during X Chromosome Inactivation
journal, June 2010
- Chow, Jennifer C.; Ciaudo, Constance; Fazzari, Melissa J.
- Cell, Vol. 141, Issue 6
Gene Action in the X-chromosome of the Mouse (Mus musculus L.)
journal, April 1961
- Lyon, Mary F.
- Nature, Vol. 190, Issue 4773
A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping
journal, December 2014
- Rao, Suhas S. P.; Huntley, Miriam H.; Durand, Neva C.
- Cell, Vol. 159, Issue 7
Dosage Compensation of the Sex Chromosomes
journal, December 2012
- Disteche, Christine M.
- Annual Review of Genetics, Vol. 46, Issue 1
Chromosome territories, nuclear architecture and gene regulation in mammalian cells
journal, April 2001
- Cremer, T.; Cremer, C.
- Nature Reviews Genetics, Vol. 2, Issue 4
Orientation-dependent Dxz4 contacts shape the 3D structure of the inactive X chromosome
journal, April 2018
- Bonora, G.; Deng, X.; Fang, H.
- Nature Communications, Vol. 9, Issue 1
A top-down analysis of Xa- and Xi-territories reveals differences of higher order structure at ≥ 20 Mb genomic length scales
journal, September 2011
- Teller, Kathrin; Illner, Doris; Thamm, Stefanie
- Nucleus, Vol. 2, Issue 5
The 3D Genome as Moderator of Chromosomal Communication
journal, March 2016
- Dekker, Job; Mirny, Leonid
- Cell, Vol. 164, Issue 6
A three-dimensional model of the yeast genome
journal, May 2010
- Duan, Zhijun; Andronescu, Mirela; Schutz, Kevin
- Nature, Vol. 465, Issue 7296