School of Engineering and Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
School of Engineering and Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
Cell Rep. 2019 Jan 2;26(1):279-292.e5. doi: 10.1016/j.celrep.2018.12.020.
Nucleosome organization has a key role in transcriptional regulation, yet the precise mechanisms establishing nucleosome locations and their effect on transcription are unclear. Here, we use an induced degradation system to screen all yeast ATP-dependent chromatin remodelers. We characterize how rapid clearance of the remodeler affects nucleosome locations. Specifically, depletion of Sth1, the catalytic subunit of the RSC (remodel the structure of chromatin) complex, leads to rapid fill-in of nucleosome-free regions at gene promoters. These changes are reversible upon reintroduction of Sth1 and do not depend on DNA replication. RSC-dependent nucleosome positioning is pivotal in maintaining promoters of lowly expressed genes free from nucleosomes. In contrast, we observe that upon acute stress, the RSC is not necessary for the transcriptional response. Moreover, RSC-dependent nucleosome positions are tightly related to usage of specific transcription start sites. Our results suggest organizational principles that determine nucleosome positions with and without RSC and how these interact with the transcriptional process.
核小体组织在转录调控中起着关键作用，但确定核小体位置的精确机制及其对转录的影响尚不清楚。在这里，我们使用诱导降解系统筛选所有酵母依赖 ATP 的染色质重塑酶。我们描述了重塑酶的快速清除如何影响核小体位置。具体来说，RSC（重塑染色质结构）复合物的催化亚基 Sth1 的耗竭会导致基因启动子处无核小体区域的快速填充。在重新引入 Sth1 后，这些变化是可逆的，并且不依赖于 DNA 复制。RSC 依赖性核小体定位对于维持低表达基因的启动子不含核小体至关重要。相比之下，我们观察到在急性应激下，RSC 对于转录反应不是必需的。此外，RSC 依赖性核小体位置与特定转录起始位点的使用密切相关。我们的研究结果表明，有和没有 RSC 决定核小体位置的组织原则，以及这些原则如何与转录过程相互作用。
