6hts

Publication Abstract from PubMed

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 machines (1) . Biochemical studies(2-4) 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 nucleosomes(5-7) 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 sliding (8) , histone exchange (9) and nucleosome spacing(10-12) remain poorly understood. Although some remodellers work as monomers (13) , others work as highly cooperative dimers(11, 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.

Structure and regulation of the human INO80-nucleosome complex.,Ayala R, Willhoft O, Aramayo RJ, Wilkinson M, McCormack EA, Ocloo L, Wigley DB, Zhang X Nature. 2018 Apr;556(7701):391-395. doi: 10.1038/s41586-018-0021-6. Epub 2018 Apr, 11. PMID:29643506^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.