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

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

Vlijm, R. (TU Delft OLD Library Operations; German Cancer Research Center)
Kim, S.H. (TU Delft BN/Cees Dekker Lab)
De Zwart, P. L.
Dalal, Y. (National Cancer Institute)
Dekker, C. (TU Delft BN/Cees Dekker Lab)

2017-02-07

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.

http://resolver.tudelft.nl/uuid:01db7382-2b78-4e55-9989-80690b490d0a

https://doi.org/10.1039/c6nr06245h

2018-01-09

2040-3364

Nanoscale, 9 (5), 1862-1870

Institutional Repository

journal article

© 2017 R. Vlijm, S.H. Kim, P. L. De Zwart, Y. Dalal, C. Dekker