Thermosensitive Nucleosome Editing Reveals the Role of DNA Sequence in Targeted Histone Variant Deposition.
Thermosensitive Nucleosome Editing Reveals the Role of DNA Sequence in Targeted Histone Variant Deposition.
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DOI：
10.1016/j.celrep.2019.12.006
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发表时间：
2020-01
期刊：
影响因子：
8.8
通讯作者：
Lu Sun;Leonidas Pierrakeas;Tailai Li;Ed Luk
中科院分区：
文献类型：
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作者：
Lu Sun;Leonidas Pierrakeas;Tailai Li;Ed Luk
在转录的准备中，染色质重塑剂SWR通过以逐步方式用H2A.Z替换两个核小体H2 A而在启动子处安装同型ZZ核小体。无核小体区（NFR）有助于将SWR募集到启动子上;这被认为是将SWR不对称地定位在+1核小体的一侧。SWR如何进入+1的相反侧以产生ZZ核小体仍不清楚。使用监测新生H2A.Z的亚核小体位置的生化测定，我们发现NFR募集的SWR切换侧以将H2A.Z插入不对称定位的核小体中;然而，在降低的温度下，H2A.Z插入逐渐偏向一侧。我们发现，含有G/C序列（>3个连续的G或C核苷酸）的16-bp元件足以促进H2A.Z插入。由于酵母中富含H2 A. Z的+1核小体具有更多的G/C运行，我们提出核小体编辑是一个可以由基因组硬编码的热敏过程。
In preparation for transcription, the chromatin remodeler SWR installs homotypic ZZ nucleosomes at promoters by replacing the two nucleosomal H2A with H2A.Z in a stepwise manner. Nucleosome-free regions (NFRs) help recruit SWR to promoters; this is thought to position SWR asymmetrically on one side of the +1 nucleosome. How SWR accesses the opposite side of +1 to generate a ZZ nucleosome remains unclear. Using biochemical assays that monitor the sub-nucleosomal position of nascent H2A.Z, we find that NFR-recruited SWR switches sides to insert H2A.Z into asymmetrically positioned nucleosomes; however, at decreasing temperatures, H2A.Z insertion becomes progressively biased for one side. We find that a 16-bp element containing G/C runs (>3 consecutive G or C nucleotides) is sufficient to promote H2A.Z insertion. Because H2A.Z-rich +1 nucleosomes in yeast have more G/C runs, we propose that nucleosome editing is a thermosensitive process that can be hard coded by the genome.