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Structure and regulation of the human INO80–nucleosome complex
DOI:
10.1038/s41586-018-0021-6
Authors:
Rafael
Ayala
(Imperial College London)
,
Oliver
Willhoft
(Imperial College London)
,
Ricardo J.
Aramayo
(Imperial College London)
,
Martin
Wilkinson
(Imperial College London)
,
Elizabeth A.
Mccormack
(Imperial College London)
,
Lorraine
Ocloo
(Imperial College London)
,
Dale B.
Wigley
(Imperial College London)
,
Xiaodong
Zhang
(Imperial College London)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Nature
, VOL 556
, PAGES 391 - 395
State:
Published (Approved)
Published:
April 2018
Diamond Proposal Number(s):
14769
Abstract: Access to DNA within nucleosomes is required for a variety of processes in cells including transcription, replication and repair. Consequently, cells encode multiple systems that remodel nucleosomes. These complexes can be simple, involving one or a few protein subunits, or more complicated multi-subunit machines1. Biochemical studies2,3,4 have placed the motor domains of several chromatin remodellers in the superhelical location 2 region of the nucleosome. Structural studies of yeast Chd1 and Snf2—a subunit in the complex with the capacity to remodel the structure of chromatin (RSC)—in complex with nucleosomes5,6,7 have provided insights into the basic mechanism of nucleosome sliding performed by these complexes. However, how larger, multi-subunit remodelling complexes such as INO80 interact with nucleosomes and how remodellers carry out functions such as nucleosome sliding8, histone exchange9 and nucleosome spacing10,11,12 remain poorly understood. Although some remodellers work as monomers13, others work as highly cooperative dimers11, 14, 15. Here we present the structure of the human INO80 chromatin remodeller with a bound nucleosome, which reveals that INO80 interacts with nucleosomes in a previously undescribed manner: the motor domains are located on the DNA at the entry point to the nucleosome, rather than at superhelical location 2. The ARP5–IES6 module of INO80 makes additional contacts on the opposite side of the nucleosome. This arrangement enables the histone H3 tails of the nucleosome to have a role in the regulation of the activities of the INO80 motor domain—unlike in other characterized remodellers, for which H4 tails have been shown to regulate the motor domains.
Journal Keywords: Chromatin remodelling; Cryoelectron microscopy
Subject Areas:
Biology and Bio-materials
Diamond Offline Facilities:
Electron Bio-Imaging Centre (eBIC)
Instruments:
Krios II-Titan Krios II at Diamond