Energy-driven genome regulation by ATP-dependent chromatin remodellers

Sebastian Eustermann, Avinash B. Patel, Karl-Peter Hopfner, Yuan He, Philipp Korber (Published online 2023 Dec 11) Energy-driven genome regulation by ATP-dependent chromatin remodellers. Nature Reviews Molecular Cell Biology.  https://doi.org/10.1038/s41580-023-00683-y

A comprehensive review on ATP-dependent chromatin remodelers published in Nature Reviews Molecular Cell Biology by SFB1064 project leaders Philipp Korber and Karl-Peter Hopfner in collaboration with first author Sebastian Eustermann (formerly postdoc in the Hopfner group and now group leader at EMBL, Heidelberg) and Yuan He (Northwestern University, USA) and his postdoc Avinash Patel. This review features animations that were produced by Janet Iwasa’s animation lab (University of Utah, USA) based on high-resolution structures and show chromatin remodelers in action. The production costs for these animations were co-funded by the SFB1064.

Abstract cited directly from the review article:

The packaging of DNA into chromatin in eukaryotes regulates gene transcription, DNA replication and DNA repair. ATP-dependent chromatin remodelling enzymes (re)arrange nucleosomes at the first level of chromatin organization. Their Snf2-type motor ATPases alter histone–DNA interactions through a common DNA translocation mechanism. Whether remodeller activities mainly catalyse nucleosome dynamics or accurately co-determine nucleosome organization remained unclear. In this Review, we discuss the emerging mechanisms of chromatin remodelling: dynamic remodeller architectures and their interactions, the inner workings of the ATPase cycle, allosteric regulation and pathological dysregulation. Recent mechanistic insights argue for a decisive role of remodellers in the energy-driven selforganization of chromatin, which enables both stability and plasticity of genome regulation — for example, during development and stress. Different remodellers, such as members of the SWI/SNF, ISWI, CHD and INO80 families, process (epi)genetic information through specific mechanisms into distinct functional outputs. Combinatorial assembly of remodellers and their interplay with histone modifications, histone variants, DNA sequence or DNA-bound transcription factors regulate nucleosome mobilization or eviction or histone exchange. Such input–output relationships determine specific nucleosome positions and compositions with distinct DNA accessibilities and mediate differential genome regulation. Finally, remodeller genes are often mutated in diseases characterized by genome dysregulation, notably in cancer, and we discuss their physiological relevance.

Featured animations can also be viewed here on our SFB 1064 website.