Abstract
Nucleosomes form arrays with even spacing between them in virtually all eukaryotes;however, their biogenesis is incompletely understood. Here the authors show that nucleosome density and DNA sequence along with the Ino80 chromatin remodeling complex play a role in nucleosome array formation in yeast and that the transcriptional machinery disrupts evenly-spaced nucleosomes. 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.
| Item Type: | Journal article |
|---|---|
| Faculties: | Medicine |
| Subjects: | 600 Technology > 610 Medicine and health |
| Language: | English |
| Item ID: | 102165 |
| Date Deposited: | 05. Jun 2023, 15:39 |
| Last Modified: | 17. Oct 2023, 15:10 |
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