Department of Biochemistry and Molecular Pharmacology
Amino Acids, Peptides, and Proteins | Biochemistry | Molecular Biology | Structural Biology
The fundamental molecular determinants by which ATP-dependent chromatin remodelers organize nucleosomes across eukaryotic genomes remain largely elusive. Here, chromatin reconstitutions on physiological, whole-genome templates reveal how remodelers read and translate genomic information into nucleosome positions. Using the yeast genome and the multi-subunit INO80 remodeler as a paradigm, we identify DNA shape/mechanics encoded signature motifs as sufficient for nucleosome positioning and distinct from known DNA sequence preferences of histones. INO80 processes such information through an allosteric interplay between its core- and Arp8-modules that probes mechanical properties of nucleosomal and linker DNA. At promoters, INO80 integrates this readout of DNA shape/mechanics with a readout of co-evolved sequence motifs via interaction with general regulatory factors bound to these motifs. Our findings establish a molecular mechanism for robust and yet adjustable +1 nucleosome positioning and, more generally, remodelers as information processing hubs that enable active organization and allosteric regulation of the first level of chromatin.
Biochemistry, genome information processing, chromatin
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DOI of Published Version
bioRxiv 2020.11.03.366690; doi: https://doi.org/10.1101/2020.11.03.366690. Link to preprint on bioRxiv.
Oberbeckmann E, Krietenstein N, Niebauer V, Wang Y, Schall K, Moldt M, Straub T, Rohs R, Hopfner K, Korber P, Eustermann S. (2020). Genome information processing by the INO80 chromatin remodeler positions nucleosomes [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/2020.11.03.366690. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1842
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