Structural basis of nucleosome disassembly and reassembly by RNAPII elongation complex with FACT
Structural basis of nucleosome disassembly and reassembly by RNAPII elongation complex with FACT
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DOI：
10.1126/science.abp9466
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发表时间：
2022-09-09
期刊：
影响因子：
56.9
通讯作者：
Sekine, Shun-ichi
中科院分区：
文献类型：
--
作者：
Ehara, Haruhiko;Kujirai, Tomoya;Sekine, Shun-ichi
在基因转录过程中，RNA聚合酶II（RNAPII）穿过染色质中的核小体，但其机制仍然难以捉摸。使用冷冻电子显微镜，我们得到的RNAPII延伸复合物（EC）通过核小体的转录延伸因子Spt 6，Spn 1，Elf 1，Spt 4/5，和Paf 1C和组蛋白伴侣FACT（促进染色质转录）的存在下的结构。这些结构显示了EC进展的快照，DNA介导下游核小体解体，然后在EC上游重新组装，这是由FACT促进的。FACT动态地适应连续发生的亚核小体中间体，与EC形成界面。Spt 6、Spt 4/5和Paf 1C在EC DNA出口位点形成“摇篮”，并支持上游核小体重组。这些结构解释了EC穿越核小体同时保持染色质结构和表观遗传信息的机制。
During gene transcription, RNA polymerase II (RNAPII) traverses nucleosomes in chromatin, but the mechanism has remained elusive. Using cryo-electron microscopy, we obtained structures of the RNAPII elongation complex (EC) passing through a nucleosome in the presence of the transcription elongation factors Spt6, Spn1, Elf1, Spt4/5, and Paf1C and the histone chaperone FACT (facilitates chromatin transcription). The structures show snapshots of EC progression on DNA mediating downstream nucleosome disassembly, followed by its reassembly upstream of the EC, which is facilitated by FACT. FACT dynamically adapts to successively occurring subnucleosome intermediates, forming an interface with the EC. Spt6, Spt4/5, and Paf1C form a "cradle" at the EC DNA-exit site and support the upstream nucleosome reassembly. These structures explain the mechanism by which the EC traverses nucleosomes while maintaining the chromatin structure and epigenetic information.