Thermosensitive Nucleosome Editing Reveals the Role of DNA Sequence in Targeted Histone Variant Deposition.,Cell Reports

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Thermosensitive Nucleosome Editing Reveals the Role of DNA Sequence in Targeted Histone Variant Deposition.
Cell Reports ( IF 7.5 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.celrep.2019.12.006
Lu Sun ₁ , Leonidas Pierrakeas ₁ , Tailai Li ₁ , Ed Luk ₂

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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.

中文翻译：

热敏核小体编辑揭示了DNA序列在靶向组蛋白变异沉积中的作用。

在准备转录时，染色质重塑剂SWR通过以H2A.Z逐步取代两个核小体H2A在启动子上安装同型ZZ核小体。无核小体区域（NFR）帮助将SWR募集到启动子中；这被认为是将SWR不对称地置于+1核小体的一侧。SWR如何访问+1的另一侧以生成ZZ核小体尚不清楚。使用生化测定法监测新生H2A.Z的亚核小体位置，我们发现NFR招募的SWR切换侧面以将H2A.Z插入不对称定位的核小体中。但是，在温度降低的情况下，H2A.Z的插入会逐渐向一侧倾斜。我们发现，包含G / C运行的16 bp元素（> 3个连续的G或C核苷酸）足以促进H2A.Z插入。因为是H2A。

更新日期：2020-01-07

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