Laboratory of Chromatin Structure and Function, Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
RIKEN Center for Biosystems Dynamics Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
Nat Commun. 2022 Nov 26;13(1):7287. doi: 10.1038/s41467-022-35003-z.
In chromatin, linker histone H1 binds to nucleosomes, forming chromatosomes, and changes the transcription status. However, the mechanism by which RNA polymerase II (RNAPII) transcribes the DNA in the chromatosome has remained enigmatic. Here we report the cryo-electron microscopy (cryo-EM) structures of transcribing RNAPII-chromatosome complexes (forms I and II), in which RNAPII is paused at the entry linker DNA region of the chromatosome due to H1 binding. In the form I complex, the H1 bound to the nucleosome restricts the linker DNA orientation, and the exit linker DNA is captured by the RNAPII DNA binding cleft. In the form II complex, the RNAPII progresses a few bases ahead by releasing the exit linker DNA from the RNAPII cleft, and directly clashes with the H1 bound to the nucleosome. The transcription elongation factor Spt4/5 masks the RNAPII DNA binding region, and drastically reduces the H1-mediated RNAPII pausing.
在染色质中，连接组蛋白 H1 结合核小体，形成染色质小体，并改变转录状态。然而，RNA 聚合酶 II (RNAPII) 在染色质小体中转录 DNA 的机制仍然是个谜。在这里，我们报告了正在转录的 RNAPII-染色质小体复合物（形式 I 和 II）的低温电子显微镜 (cryo-EM) 结构，由于 H1 的结合，RNAPII 在染色质小体的入口连接 DNA 区域暂停。在形式 I 复合物中，与核小体结合的 H1 限制了连接 DNA 的方向，而出口连接 DNA 被 RNAPII DNA 结合裂缝捕获。在形式 II 复合物中，RNAPII 通过从 RNAPII 裂缝中释放出口连接 DNA 向前推进几个碱基，并与与核小体结合的 H1 直接发生冲突。转录延伸因子 Spt4/5 掩盖了 RNAPII DNA 结合区域，并大大减少了 H1 介导的 RNAPII 暂停。
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