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Issue 5, 2017
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The supercoiling state of DNA determines the handedness of both H3 and CENP-A nucleosomes

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Abstract

Nucleosomes form the unit structure of the genome in eukaryotes, thereby constituting a fundamental tenet of chromatin biology. In canonical nucleosomes, DNA wraps around the histone octamer in a left-handed toroidal ramp. Here, in single-molecule magnetic tweezers studies of chaperone-assisted nucleosome assembly, we show that the handedness of the DNA wrapping around the nucleosome core is intrinsically ambidextrous, and depends on the pre-assembly supercoiling state of the DNA, i.e., it is not uniquely determined by the octameric histone core. Nucleosomes assembled onto negatively supercoiled DNA are found to exhibit a left-handed conformation, whereas assembly onto positively supercoiled DNA results in right-handed nucleosomes. This intrinsic flexibility to adopt both chiralities is observed both for canonical H3 nucleosomes, and for centromere-specific variant CENP-A nucleosomes. These data support recent advances suggesting an intrinsic adaptability of the nucleosome, and provide insights into how nucleosomes might rapidly re-assemble after cellular processes that generate positive supercoiling in vivo.

Graphical abstract: The supercoiling state of DNA determines the handedness of both H3 and CENP-A nucleosomes

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Publication details

The article was received on 06 Aug 2016, accepted on 08 Jan 2017 and first published on 09 Jan 2017


Article type: Paper
DOI: 10.1039/C6NR06245H
Citation: Nanoscale, 2017,9, 1862-1870
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    The supercoiling state of DNA determines the handedness of both H3 and CENP-A nucleosomes

    R. Vlijm, S. H. Kim, P. L. De Zwart, Y. Dalal and C. Dekker, Nanoscale, 2017, 9, 1862
    DOI: 10.1039/C6NR06245H

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