Mechanisms of INO80 remodeling

Abstract

The INO80 complex is an evolutionarily conserved ATP-dependent chromatin remodeler with central roles in transcription, DNA replication, and genome maintenance. INO80 is unusual among chromatin remodelers in its ability to space nucleosomes, position nucleosomes in a DNA-shape-dependent manner, and exchange H2A-H2B dimers. Recent structural and biochemical studies have provided new insight into how these diverse activities are generated and regulated. Here, we discuss evidence that INO80 remodeling is controlled by two distinct forms of DNA sensing. The Arp8 module senses extranucleosomal DNA length and regulates nucleosome spacing, whereas the mechanical properties of DNA within the nucleosome influence DNA translocation and sequence-dependent nucleosome positioning. We further discuss a model in which INO80′s ATPase activity initiates entry-side DNA unwrapping and movement, generating a DNA bulge that propagates across the histone-octamer surface. Conformational changes in the Arp5 module may couple ATPase-driven DNA translocation to these changes in histone-DNA interactions. Together, these findings provide a mechanistic framework for understanding how INO80 integrates linker-DNA sensing, DNA mechanics, and ATP-dependent remodeling to generate distinct chromatin structures.