RT Journal Article SR Electronic T1 The biogenesis and function of nucleosome arrays JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.02.10.429500 DO 10.1101/2021.02.10.429500 A1 Ashish Kumar Singh A1 Tamás Schauer A1 Lena Pfaller A1 Tobias Straub A1 Felix Mueller-Planitz YR 2021 UL http://biorxiv.org/content/early/2021/02/10/2021.02.10.429500.abstract AB Numerous chromatin remodeling enzymes position nucleosomes in eukaryotic cells. Aside from these factors, transcription, DNA sequence, and statistical positioning of nucleosomes also shapes the nucleosome landscape. Precise contributions of these processes remain unclear due to their functional redundancy in vivo. By incisive genome engineering, we radically decreased their redundancy in Saccharomyces cerevisiae. The transcriptional machinery is strongly disruptive of evenly spaced nucleosomes, and proper nucleosome density and DNA sequence critical for their biogenesis. The INO80 remodeling complex spaces nucleosomes in vivo and positions the first nucleosome over genes in an H2A.Z-independent fashion. INO80 requires its Arp8 subunit but unexpectedly not the Nhp10 module for spacing. Spaced nucleosomes prevent cryptic transcription and protect cells against genotoxic stress such as DNA damage, recombination and transpositions. We derive a unifying model of the biogenesis of the nucleosome landscape and suggest that it evolved not only to regulate but also to protect the genome.Competing Interest StatementThe authors have declared no competing interest.