Numerous chromatin remodeling enzymes position nucleosomes in eukaryotic cells. Aside from these factors, transcription, DNA sequence, and statistical positioning of nucleosomes also shape the nucleosome landscape. The 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 strongly disrupts evenly spaced nucleosomes. Proper nucleosome density and DNA sequence are critical for their biogenesis. The INO80 remodeling complex helps space 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. Cells with irregularly spaced nucleosomes suffer from genotoxic stress including DNA damage, recombination and transpositions. We derive a model of the biogenesis of the nucleosome landscape and suggest that it evolved not only to regulate but also to protect the genome.

许多染色质重塑酶定位真核细胞中的核小体。除了这些因素之外，核小体的转录、DNA 序列和统计定位也塑造了核小体景观。由于它们在体内的功能冗余，这些过程的确切贡献仍不清楚。通过精辟的基因组工程，我们从根本上减少了它们在酿酒酵母中的冗余. 转录机制强烈破坏均匀分布的核小体。适当的核小体密度和 DNA 序列对其生物发生至关重要。INO80 重塑复合物有助于体内核小体的空间，并以 H2A.Z 独立方式将第一个核小体定位在基因上。INO80 需要其 Arp8 子单元，但出乎意料的是不需要 Nhp10 模块来进行间隔。具有不规则间隔核小体的细胞遭受遗传毒性应激，包括 DNA 损伤、重组和转座。我们推导出核小体景观的生物发生模型，并表明它的进化不仅是为了调节，而且是为了保护基因组。