Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory for Tumor Invasion and Metastasis, Capital Medical University, Beijing, 100069, China.
National Laboratory for Condensed Matter Physics and Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, 100190, China.
Nat Commun. 2023 Feb 10;14(1):741. doi: 10.1038/s41467-023-36467-3.
Histone H2B mono-ubiquitination at lysine 120 (ubH2B) has been found to regulate transcriptional elongation by collaborating with the histone chaperone FACT (Facilitates Chromatin Transcription) and plays essential roles in chromatin-based transcriptional processes. However, the mechanism of how ubH2B directly collaborates with FACT at the nucleosome level still remains elusive. In this study, we demonstrate that ubH2B impairs the mechanical stability of the nucleosome and helps to recruit FACT by enhancing the binding of FACT on the nucleosome. FACT prefers to bind and deposit H2A-ubH2B dimers to form an intact nucleosome. Strikingly, the preferable binding of FACT on ubH2B-nucleosome greatly enhances nucleosome stability and maintains its integrity. The stable altered nucleosome state obtained by ubH2B and FACT provides a key platform for gene transcription, as revealed by genome-wide and time-course ChIP-qPCR analyses. Our findings provide mechanistic insights of how ubH2B directly collaborates with FACT to regulate nucleosome dynamics for gene transcription.
组蛋白 H2B 赖氨酸 120 单泛素化 (ubH2B) 已被发现通过与组蛋白伴侣 FACT（促进染色质转录）协作来调节转录延伸，并在基于染色质的转录过程中发挥重要作用。然而，ubH2B 如何在核小体水平上直接与 FACT 协作的机制仍然难以捉摸。在这项研究中，我们证明 ubH2B 会损害核小体的机械稳定性，并通过增强 FACT 在核小体上的结合来帮助招募 FACT。FACT 更喜欢结合并沉积 H2A-ubH2B 二聚体以形成完整的核小体。引人注目的是，FACT 在 ubH2B-核小体上的优先结合极大地增强了核小体的稳定性并保持其完整性。通过 ubH2B 和 FACT 获得的稳定改变的核小体状态为基因转录提供了一个关键平台，这一点通过全基因组和时程 ChIP-qPCR 分析得到了揭示。我们的研究结果提供了 ubH2B 如何直接与 FACT 协作来调节核小体动力学以进行基因转录的机制见解。
