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Three-dimensional positioning and structure of chromosomes in a human prophase nucleus

Chen, B; Yusuf, M; Hashimoto, T; Estandarte, AK; Thompson, G; Robinson, I; (2017) Three-dimensional positioning and structure of chromosomes in a human prophase nucleus. Science Advances , 3 (7) , Article e1602231. 10.1126/sciadv.1602231. Green open access

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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 the chromatids, whose occupied volumes are almost fully accounted for by the DNA and known chromosomal proteins. We also propose a potential new method of identifying human chromosomes in three dimensions, on the basis of the measurements of their 3D morphology.

Type: Article
Title: Three-dimensional positioning and structure of chromosomes in a human prophase nucleus
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/sciadv.1602231
Publisher version: http://doi.org/10.1126/sciadv.1602231
Language: English
Additional information: Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > London Centre for Nanotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10025274
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