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

Chen, Bo; Yusuf, Mohammed; Hashimoto, Teruo; Estandarte, Ana Katrina; Thompson, George; Robinson, Ian

doi:10.1126/sciadv.1602231

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

Journal Article · Fri Jul 21 00:00:00 EDT 2017 · Science Advances

DOI:https://doi.org/10.1126/sciadv.1602231· OSTI ID:1372455

Chen, Bo ^[1]; Yusuf, Mohammed ^[2]; Hashimoto, Teruo ^[3]; Estandarte, Ana Katrina ^[2]; Thompson, George ^[3]; Robinson, Ian ^[4]

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)

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.

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Research Organization:: Brookhaven National Laboratory (BNL), Upton, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: SC00112704

OSTI ID:: 1372455

Report Number(s):: BNL-114059-2017-JA; R&D Project: PO011; KC0201060

Journal Information:: Science Advances, Vol. 3, Issue 7; ISSN 2375-2548

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 25 works

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