Genome-wide Rules of Nucleosome Phasing in Drosophila

Regular successions of positioned nucleosomes, or phased nucleosome arrays (PNAs), are predominantly known from transcriptional start sites (TSSs). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to...

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Bibliographic Details
Published in:Molecular cell 2018-11, Vol.72 (4), p.661-672.e4
Main Authors: Baldi, Sandro, Jain, Dhawal S., Harpprecht, Lisa, Zabel, Angelika, Scheibe, Marion, Butter, Falk, Straub, Tobias, Becker, Peter B.
Format: Article
Language:English
Subjects:
chromatin
linker DNA
micrococcal nuclease
nucleosome remodeling
regularity
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Summary:Regular successions of positioned nucleosomes, or phased nucleosome arrays (PNAs), are predominantly known from transcriptional start sites (TSSs). It is unclear whether PNAs occur elsewhere in the genome. To generate a comprehensive inventory of PNAs for Drosophila, we applied spectral analysis to nucleosome maps and identified thousands of PNAs throughout the genome. About half of them are not near TSSs and are strongly enriched for an uncharacterized sequence motif. Through genome-wide reconstitution of physiological chromatin in Drosophila embryo extracts, we uncovered the molecular basis of PNA formation. We identified Phaser, an unstudied zinc finger protein that positions nucleosomes flanking the motif. It also revealed how the global activity of the chromatin remodelers CHRAC/ACF, together with local barrier elements, generates islands of regular phasing throughout the genome. Our work demonstrates the potential of chromatin assembly by embryo extracts as a powerful tool to reconstitute chromatin features on a global scale in vitro. [Display omitted] •Phased nucleosome arrays are mapped genome-wide in Drosophila•A DNA motif strongly associated with phased arrays in flies and mice is identified•Phaser, a previously uncharacterized protein, binds this motif•Phased arrays are generated by local barrier elements and chromatin remodelers Patches of evenly spaced nucleosomes mark regulatory elements in the genome. Baldi et al. comprehensively map such phased arrays throughout the Drosophila genome. By reconstituting phased arrays in a cell-free system, they identify principles of array formation and the Phaser protein as a major determinant of phased arrays.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2018.09.032