Crosstalk within a functional INO80 complex dimer regulates nucleosome sliding.

Oliver Willhoft,Lorraine Ocloo,Xiaodong Zhang,Rohan Bythell-Douglas,Ricardo J Aramayo,Elizabeth A McCormack,Dale B Wigley

doi:10.7554/elife.25782

Abstract

Several chromatin remodellers have the ability to space nucleosomes on DNA. For ISWI remodellers, this involves an interplay between H4 histone tails, the AutoN and NegC motifs of the motor domains that together regulate ATPase activity and sense the length of DNA flanking the nucleosome. By contrast, the INO80 complex also spaces nucleosomes but is not regulated by H4 tails and lacks the AutoN and NegC motifs. Instead nucleosome sliding requires cooperativity between two INO80 complexes that monitor DNA length simultaneously on either side of the nucleosome during sliding. The C-terminal domain of the human Ino80 subunit (Ino80CTD) binds cooperatively to DNA and dimerisation of these domains provides crosstalk between complexes. ATPase activity, rather than being regulated, instead gradually becomes uncoupled as nucleosome sliding reaches an end point and this is controlled by the Ino80CTD. A single active ATPase motor within the dimer is sufficient for sliding.

Highlights

Chromatin remodelling complexes are important regulators of the chromatin landscape and have vital roles in transcription, DNA damage repair and replication (Clapier and Cairns, 2009)
We show that the hINO80 complex, like ACF, appears to be able to centre nucleosomes on DNA fragments, this ability is due to being able to sense when the nucleosome is within 50 base pairs from a DNA end
Proteins that assist nucleosome sliding are characterised by movement either towards or away from DNA ends

Summary

Introduction

Chromatin remodelling complexes are important regulators of the chromatin landscape and have vital roles in transcription, DNA damage repair and replication (Clapier and Cairns, 2009) Many of these complexes vary in complexity from one or a few subunits (e.g. CHD1 [Delmas et al, 1993] or ACF [Ito et al, 1997]) to larger systems with more than a dozen subunits (e.g. INO80 [Shen et al, 2000] and RSC [Cairns et al, 1996]). How the 147 base pair wrap slides around the histone core is still largely a mystery and regulation of the process is even more poorly understood It is unclear which aspects of mechanism are conserved between these highly variable systems and which ones are specific to different complexes.

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Conclusion