Partially assembled nucleosome structures at atomic detail
Onufriev, Alexey V.
MetadataShow full item record
Evidence is now overwhelming that partially assembled states of the nucleosome are as important as the canonical structure for the understanding of how DNA accessibility is regulated in cells. We use a combination of atomistic simulation and Atomic Force Microscopy (AFM) to propose models of key partially assembled structures of the nucleosome at atomic detail: the heaxasome ((H3·H4)2·(H2A·H2B)), the tetrasome ((H3·H4)2), and the disome (H3·H4). Despite large-scale fluctuations of the “free” DNA not in direct contact with the histones in these structures, the histone-DNA contacts are stable, establishing the basis for interpretation of the role of these structures in providing variable degree of DNA accessibility within the chromatin. We show how the atomistically detailed partially assembled nucleosome structures can be used to interpret experimental observations, both in-vitro and in-vivo. Specifically, interpretation of FRET, AFM, (and SAXS) experiments under conditions where partially assembled nucleosome states are expected is greatly facilitated by the availability of atomic- resolution structural ensembles of these states. We also suggest an alternative interpretation of a recent genome-wide study that investigated types of DNA protection in classical “active” chromatin, lending support for the transcription speed-up scenario that involves partially assembled sub-nucleosome structures.