Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome.

David G Norman,Helder Ferreira,Hassane El-Mkami,Amanda L Hughes,Ramasubramanian Sundaramoorthy,Tom Owen-Hughes

doi:10.7554/elife.35720

Abstract

ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here, we present structures of the Saccharomyces cerevisiae Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.

Highlights

The extended family of ATPases related to the yeast Snf2 protein acts to alter DNA-protein interactions (Flaus et al, 2006; Narlikar et al, 2013)
Nucleosomes were prepared in which histone H3 K36 was alkylated to mimic trimethylation (Figure 1—figure supplement 1) and H2B cross-linked to ubiquitin (Figure 1—figure supplement 2)
Chd1 predominantly contacts the nucleosome via contacts with DNA, via the DNA binding domain (DNABD) in the linker and ATPase lobes at SHL2; contacts with histones are limited to the histone H3 and H4 N-terminal regions discussed below

Summary

Introduction

The extended family of ATPases related to the yeast Snf protein acts to alter DNA-protein interactions (Flaus et al, 2006; Narlikar et al, 2013). They act on a diverse range of substrates. The yeast Chd protein is a member of this protein family and acts to organise nucleosomes over coding regions (Gkikopoulos et al, 2011; Ocampo et al, 2016; Pointner et al, 2012; Tran et al, 2000). The partially redundant functions of Chd and Isw in organising nucleosomes over coding regions are in turn required to prevent histone exchange and non-coding transcription (Hennig et al, 2012; Radman-Livaja et al, 2012; Smolle et al, 2012)

Methods

Results

Conclusion