Megadalton chromatin remodelers: common principles for versatile functions

摘要

ATP-dependent chromatin remodelers are enigmatic macromolecular machines that govern the arrangement and composition of nucleosomes across eukaryotic genomes. Here, we review the recent breakthrough provided by cryoelectron microscopy that reveal the first high-resolution insights into all four families of remodelers. We highlight the emerging structural and mechanistic principles with a particular focus on multi-subunit SWI/SNF and INO80/SWR1 complexes. A conserved architecture comprising a motor, rotor, stator and grip suggests a unifying mechanism for how stepwise DNA translocation enables large scale reconfigurations of nucleosomes. A molecular circuitry involving the nuclear actin containing module establishes a framework for understanding allosteric regulation. Remodelers emerge as programable hubs that enable differential processing of genetic and epigenetic information in response to the physiological state of a cell.