<br>组蛋白 H2B 泛素化和 H3K79me3 对转录延伸的影响,ACS Chemical Biology

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组蛋白 H2B 泛素化和 H3K79me3 对转录延伸的影响
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2023-03-01 , DOI: 10.1021/acschembio.2c00887
Mai T Huynh ₁ , Bhaswati Sengupta ₁ , Wladyslaw A Krajewski ₂ , Tae-Hee Lee ₁

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组蛋白的翻译后修饰通常通过改变核小体（真核生物的基本基因包装单位）的整体和局部稳定性来介导基因调控。我们采用半合成方法在 K34 (H2BK34ub) 和 K120 (H2BK120ub) 处引入组蛋白 H2B 泛素化以及 H3K79 三甲基化 (H3K79me3)。通过这些修饰的组蛋白，我们使用单分子 FRET 研究了它们对 RNA 聚合酶 II (Pol II) 转录延伸动力学的影响。 Pol II 在核小体内的几个位置暂停几秒到几分钟，这控制着整体转录效率。我们发现 H2B 泛素化抑制暂停并缩短核小体入口附近的暂停持续时间，而 H3K79me3 缩短暂停持续时间并增加核小体中心附近的 RNA 延伸率。我们还发现 H2BK34ub 在 Pol II 传代时促进核小体的部分重新包装。这些观察结果表明，H2B 泛素化通过诱导和稳定核小体中间体促进转录延伸并帮助维持染色质结构，并且 H3K79me3 可能通过破坏核小体局部结构的稳定性来促进 Pol II 进展。我们的结果提供了这些修饰如何通过调节蛋白网络耦合促进核小体两个不同区域中的转录并帮助维持活跃转录过程中的染色质结构的机制。

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Effects of Histone H2B Ubiquitylations and H3K79me3 on Transcription Elongation

Post-translational modifications of histone proteins often mediate gene regulation by altering the global and local stability of the nucleosome, the basic gene-packing unit of eukaryotes. We employed semisynthetic approaches to introduce histone H2B ubiquitylations at K34 (H2BK34ub) and K120 (H2BK120ub) and H3K79 trimethylation (H3K79me3). With these modified histones, we investigated their effects on the kinetics of transcription elongation by RNA polymerase II (Pol II) using single-molecule FRET. Pol II pauses at several locations within the nucleosome for a few seconds to minutes, which governs the overall transcription efficiency. We found that H2B ubiquitylations suppress pauses and shorten the pause durations near the nucleosome entry while H3K79me3 shortens the pause durations and increases the rate of RNA elongation near the center of the nucleosome. We also found that H2BK34ub facilitates partial rewrapping of the nucleosome upon Pol II passage. These observations suggest that H2B ubiquitylations promote transcription elongation and help maintain the chromatin structure by inducing and stabilizing nucleosome intermediates and that H3K79me3 facilitates Pol II progression possibly by destabilizing the local structure of the nucleosome. Our results provide the mechanisms of how these modifications coupled by a network of regulatory proteins facilitate transcription in two different regions of the nucleosome and help maintain the chromatin structure during active transcription.

更新日期：2023-03-01

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