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Jungblut, Anna; Hopfner, Karl-Peter ORCID logoORCID: https://orcid.org/0000-0002-4528-8357 and Eustermann, Sebastian (6. August 2020): Megadalton chromatin remodelers: Common principles for versatile functions. In: Current Opinion in Structural Biology, Vol. 64, 32771531: pp. 134-144 [PDF, 3MB]


ATP-dependent chromatin remodelers determine the arrangement and composition of nucleosomes across eukaryotic genomes. Understanding the mechanisms of these enigmatic, macromolecular machines promises to reveal core principles of genome regulation and maintenance. However, the complexity of remodelers and their chromosomal substrates poses a major challenge for modern structural biology. Here, we review the recent breakthrough which provided by cryo-electron microscopy 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 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 arise as programable hubs that enable differential processing of genetic and epigenetic information in response to the physiological status of a cell.

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