Three-dimensional positioning and structure of chromosomes in a human prophase nucleus
Abstract
The human genetic material is packaged into 46 chromosomes. The structure of chromosomes is known at the lowest level, where the DNA chain is wrapped around a core of eight histone proteins to form nucleosomes. Around a million of these nucleosomes, each about 11 nm in diameter and 6 nm in thickness, are wrapped up into the complex organelle of the chromosome, whose structure is mostly known at the level of visible light microscopy to form a characteristic cross shape in metaphase. However, the higher-order structure of human chromosomes, between a few tens and hundreds of nanometers, has not been well understood. We show a three-dimensional (3D) image of a human prophase nucleus obtained by serial block-face scanning electron microscopy, with 36 of the complete set of 46 chromosomes captured within it. The acquired image allows us to extract quantitative 3D structural information about the nucleus and the preserved, intact individual chromosomes within it, including their positioning and full spatial morphology at a resolution of around 50 nm in three dimensions. The chromosome positions were found, at least partially, to follow the pattern of chromosome territories previously observed only in interphase. The 3D conformation shows parallel, planar alignment of themore »
- Authors:
-
- Univ. College London, London (United Kingdom); Research Complex at Harwell, Oxfordshire (United Kingdom); Tongji Univ., Shanghai (China)
- Univ. College London, London (United Kingdom); Research Complex at Harwell, Oxfordshire (United Kingdom)
- The Univ. of Manchester, Manchester (United Kingdom)
- Univ. College London, London (United Kingdom); Research Complex at Harwell, Oxfordshire (United Kingdom); Tongji Univ., Shanghai (China); Brookhaven National Lab. (BNL), Upton, NY (United States)
- Publication Date:
- Research Org.:
- Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES)
- OSTI Identifier:
- 1372455
- Report Number(s):
- BNL-114059-2017-JA
Journal ID: ISSN 2375-2548; R&D Project: PO011; KC0201060
- Grant/Contract Number:
- SC00112704
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Science Advances
- Additional Journal Information:
- Journal Volume: 3; Journal Issue: 7; Journal ID: ISSN 2375-2548
- Publisher:
- AAAS
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY
Citation Formats
Chen, Bo, Yusuf, Mohammed, Hashimoto, Teruo, Estandarte, Ana Katrina, Thompson, George, and Robinson, Ian. Three-dimensional positioning and structure of chromosomes in a human prophase nucleus. United States: N. p., 2017.
Web. doi:10.1126/sciadv.1602231.
Chen, Bo, Yusuf, Mohammed, Hashimoto, Teruo, Estandarte, Ana Katrina, Thompson, George, & Robinson, Ian. Three-dimensional positioning and structure of chromosomes in a human prophase nucleus. United States. https://doi.org/10.1126/sciadv.1602231
Chen, Bo, Yusuf, Mohammed, Hashimoto, Teruo, Estandarte, Ana Katrina, Thompson, George, and Robinson, Ian. Fri .
"Three-dimensional positioning and structure of chromosomes in a human prophase nucleus". United States. https://doi.org/10.1126/sciadv.1602231. https://www.osti.gov/servlets/purl/1372455.
@article{osti_1372455,
title = {Three-dimensional positioning and structure of chromosomes in a human prophase nucleus},
author = {Chen, Bo and Yusuf, Mohammed and Hashimoto, Teruo and Estandarte, Ana Katrina and Thompson, George and Robinson, Ian},
abstractNote = {The human genetic material is packaged into 46 chromosomes. The structure of chromosomes is known at the lowest level, where the DNA chain is wrapped around a core of eight histone proteins to form nucleosomes. Around a million of these nucleosomes, each about 11 nm in diameter and 6 nm in thickness, are wrapped up into the complex organelle of the chromosome, whose structure is mostly known at the level of visible light microscopy to form a characteristic cross shape in metaphase. However, the higher-order structure of human chromosomes, between a few tens and hundreds of nanometers, has not been well understood. We show a three-dimensional (3D) image of a human prophase nucleus obtained by serial block-face scanning electron microscopy, with 36 of the complete set of 46 chromosomes captured within it. The acquired image allows us to extract quantitative 3D structural information about the nucleus and the preserved, intact individual chromosomes within it, including their positioning and full spatial morphology at a resolution of around 50 nm in three dimensions. The chromosome positions were found, at least partially, to follow the pattern of chromosome territories previously observed only in interphase. The 3D conformation shows parallel, planar alignment of the chromatids, whose occupied volumes are almost fully accounted for by the DNA and known chromosomal proteins. Here, we also propose a potential new method of identifying human chromosomes in three dimensions, on the basis of the measurements of their 3D morphology.},
doi = {10.1126/sciadv.1602231},
journal = {Science Advances},
number = 7,
volume = 3,
place = {United States},
year = {Fri Jul 21 00:00:00 EDT 2017},
month = {Fri Jul 21 00:00:00 EDT 2017}
}
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Works referenced in this record:
Imaging of DNA in human and plant chromosomes by high-resolution scanning electron microscopy
journal, September 1995
- Wanner, G.; Formanek, H.
- Chromosome Research, Vol. 3, Issue 6
MOLECULAR BIOLOGY: Chromatin Higher Order Folding--Wrapping up Transcription
journal, September 2002
- Horn, P. J.
- Science, Vol. 297, Issue 5588
Molecular genetics and imaging technologies for circuit-based neuroanatomy
journal, October 2009
- Arenkiel, Benjamin R.; Ehlers, Michael D.
- Nature, Vol. 461, Issue 7266
Metaphase chromosome structure: Evidence for a radial loop model
journal, August 1979
- Marsden, M. P. F.; Laemmli, U. K.
- Cell, Vol. 17, Issue 4
Communication In The Presence Of Noise
journal, February 1998
- Shannon, C. E.
- Proceedings of the IEEE, Vol. 86, Issue 2
Mitotic chromosome structure and condensation
journal, December 2006
- Belmont, Andrew S.
- Current Opinion in Cell Biology, Vol. 18, Issue 6
Revisiting higher-order and large-scale chromatin organization
journal, June 2012
- Bian, Qian; Belmont, Andrew S.
- Current Opinion in Cell Biology, Vol. 24, Issue 3
Proteome Analysis of Human Metaphase Chromosomes
journal, January 2005
- Uchiyama, Susumu; Kobayashi, Shouhei; Takata, Hideaki
- Journal of Biological Chemistry, Vol. 280, Issue 17
Cryo-EM Study of the Chromatin Fiber Reveals a Double Helix Twisted by Tetranucleosomal Units
journal, April 2014
- Song, F.; Chen, P.; Sun, D.
- Science, Vol. 344, Issue 6182
Chromosome Territories
journal, February 2010
- Cremer, T.; Cremer, M.
- Cold Spring Harbor Perspectives in Biology, Vol. 2, Issue 3
Staining and Embedding of Human Chromosomes for 3-D Serial Block-Face Scanning Electron Microscopy
journal, December 2014
- Yusuf, Mohammed; Chen, Bo; Hashimoto, Teruo
- BioTechniques, Vol. 57, Issue 6
Three-Dimensional Structure Analysis and Percolation Properties of a Barrier Marine Coating
journal, January 2013
- Chen, Bo; Guizar-Sicairos, Manuel; Xiong, Gang
- Scientific Reports, Vol. 3, Issue 1
Flow Karyotyping and Sorting of Human Chromosomes
journal, January 1986
- Gray, J. W.; Lucas, J.; Peters, D.
- Cold Spring Harbor Symposia on Quantitative Biology, Vol. 51, Issue 0
Differences in the Localization and Morphology of Chromosomes in the Human Nucleus
journal, June 1999
- Croft, Jenny A.; Bridger, Joanna M.; Boyle, Shelagh
- Journal of Cell Biology, Vol. 145, Issue 6
Architecture of metaphase chromosomes and chromosome scaffolds.
journal, January 1983
- Earnshaw, W. C.; Laemmli, U. K.
- Journal of Cell Biology, Vol. 96, Issue 1
Chromatin Structure: A Repeating Unit of Histones and DNA
journal, May 1974
- Kornberg, R. D.
- Science, Vol. 184, Issue 4139
Left-handed DNA helices
journal, February 1980
- Arnott, Struther; Chandrasekaran, Rengaswami; Birdsall, D. L.
- Nature, Vol. 283, Issue 5749
Evidence for short-range helical order in the 30-nm chromatin fibers of erythrocyte nuclei
journal, October 2011
- Scheffer, M. P.; Eltsov, M.; Frangakis, A. S.
- Proceedings of the National Academy of Sciences, Vol. 108, Issue 41
Using transmission electron microscopy and 3View to determine collagen fibril size and three-dimensional organization
journal, June 2013
- Starborg, Tobias; Kalson, Nicholas S.; Lu, Yinhui
- Nature Protocols, Vol. 8, Issue 7
Serial Block-Face Scanning Electron Microscopy to Reconstruct Three-Dimensional Tissue Nanostructure
journal, October 2004
- Denk, Winfried; Horstmann, Heinz; Harris, Kristen M.
- PLoS Biology, Vol. 2, Issue 11, Article No. e329
Kinetics of Uptake, Retention, and Radiotoxicity of 125 IUdR in Mammalian Cells: Implications of Localized Energy Deposition by Auger Processes
journal, January 1987
- Kassis, A. I.; Sastry, K. S. R.; Adelstein, S. J.
- Radiation Research, Vol. 109, Issue 1
Chromatin position in human HepG2 cells: Although being non-random, significantly changed in daughter cells
journal, February 2009
- Cvačková, Zuzana; Mašata, Martin; Staněk, David
- Journal of Structural Biology, Vol. 165, Issue 2
Size-Dependent Positioning of Human Chromosomes in Interphase Nuclei
journal, July 2000
- Sun, Hui Bin; Shen, Jin; Yokota, Hiroki
- Biophysical Journal, Vol. 79, 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
Crystal structure of the nucleosome core particle at 2.8 Å resolution
journal, September 1997
- Luger, Karolin; Mäder, Armin W.; Richmond, Robin K.
- Nature, Vol. 389, Issue 6648
Human mitotic chromosomes consist predominantly of irregularly folded nucleosome fibres without a 30-nm chromatin structure: Human mitotic chromosomes consist of nucleosome fibres
journal, February 2012
- Nishino, Yoshinori; Eltsov, Mikhail; Joti, Yasumasa
- The EMBO Journal, Vol. 31, Issue 7
Karyotyping human chromosomes by combinatorial multi-fluor FISH
journal, April 1996
- Speicher, Michael R.; Ballard, Stephen Gwyn; Ward, David C.
- Nature Genetics, Vol. 12, Issue 4
Chromosome order in HeLa cells changes during mitosis and early G1, but is stably maintained during subsequent interphase stages
journal, February 2003
- Walter, Joachim; Schermelleh, Lothar; Cremer, Marion
- Journal of Cell Biology, Vol. 160, Issue 5
Chromatin Structure: Deduced from a Minichromosome
journal, March 1975
- Griffith, J. D.
- Science, Vol. 187, Issue 4182
Quantitative karyotyping of human chromosomes by dual beam flow cytometry.
journal, December 1982
- Langlois, R. G.; Yu, L. C.; Gray, J. W.
- Proceedings of the National Academy of Sciences, Vol. 79, Issue 24
Orchestrating nuclear envelope disassembly and reassembly during mitosis
journal, March 2009
- Güttinger, Stephan; Laurell, Eva; Kutay, Ulrike
- Nature Reviews Molecular Cell Biology, Vol. 10, Issue 3
Communication in the Presence of Noise
journal, January 1949
- Shannon, C. E.
- Proceedings of the IRE, Vol. 37, Issue 1
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journal, September 2018
- Maass, Philipp G.; Barutcu, A. Rasim; Rinn, John L.
- Journal of Cell Biology, Vol. 218, Issue 1
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journal, January 2020
- Huang, Ying; Chen, Bo; Duan, Jian
- Angewandte Chemie, Vol. 132, Issue 9
Use of 3D imaging for providing insights into high-order structure of mitotic chromosomes
journal, September 2018
- Yusuf, Mohammed; Kaneyoshi, Kohei; Fukui, Kiichi
- Chromosoma, Vol. 128, Issue 1
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- Materials, Vol. 12, Issue 3
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- Bai, Xue; Chen, Bo; Yang, Fei
- RSC Advances, Vol. 8, Issue 59
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- Huang, Ying; Chen, Bo; Duan, Jian
- Angewandte Chemie International Edition, Vol. 59, Issue 9