RT Journal Article SR Electronic T1 Three-dimensional positioning and structure of chromosomes in a human prophase nucleus JF Science Advances JO Sci Adv FD American Association for the Advancement of Science SP e1602231 DO 10.1126/sciadv.1602231 VO 3 IS 7 A1 Chen, Bo A1 Yusuf, Mohammed A1 Hashimoto, Teruo A1 Estandarte, Ana Katrina A1 Thompson, George A1 Robinson, Ian YR 2017 UL http://advances.sciencemag.org/content/3/7/e1602231.abstract AB 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.