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Oberbeckmann, Elisa; Niebauer, Vanessa; Watanabe, Shinya; Farnung, Lucas; Moldt, Manuela; Schmid, Andrea; Cramer, Patrick; Peterson, Craig L.; Eustermann, Sebastian; Hopfner, Karl-Peter und Korber, Philipp (2021): Ruler elements in chromatin remodelers set nucleosome array spacing and phasing. In: Nature Communications, Bd. 12, Nr. 1, 3232

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Abstract

Arrays of regularly spaced nucleosomes dominate chromatin and are often phased by alignment to reference sites like active promoters. How the distances between nucleosomes (spacing), and between phasing sites and nucleosomes are determined remains unclear, and specifically, how ATP-dependent chromatin remodelers impact these features. Here, we used genome-wide reconstitution to probe how Saccharomyces cerevisiae ATP-dependent remodelers generate phased arrays of regularly spaced nucleosomes. We find that remodelers bear a functional element named the 'ruler' that determines spacing and phasing in a remodeler-specific way. We use structure-based mutagenesis to identify and tune the ruler element residing in the Nhp10 and Arp8 modules of the INO80 remodeler complex. Generally, we propose that a remodeler ruler regulates nucleosome sliding direction bias in response to (epi)genetic information. This finally conceptualizes how remodeler-mediated nucleosome dynamics determine stable steady-state nucleosome positioning relative to other nucleosomes, DNA bound factors, DNA ends and DNA sequence elements. Although chromatin remodelers have been shown to align nucleosome arrays to barriers and to generate spacing regularity among nucleosomes within arrays, it has remained unclear how the distance to barrier and the spacing length are determined in absolute terms. Here, the authors reveal that remodelers contain a 'ruler' element that sets remodeler-specific alignment and spacing distances when generating nucleosome arrays.

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