Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
Curr Opin Struct Biol. 2023 Oct;82:102649. doi: 10.1016/j.sbi.2023.102649. Epub 2023 Jul 8.
Post-translational modification of histones plays a central role in regulating transcription. Methylation of histone H3 at lysines 4 (H3K4) and 79 (H3K79) play roles in activating transcription whereas methylation of H3K27 is a repressive mark. These modifications, in turn, depend upon prior monoubiquitination of specific histone residues in a phenomenon known as histone crosstalk. Earlier work had provided insights into the mechanism by which monoubiquitination histone H2BK120 stimulates H3K4 methylation by COMPASS/MLL1 and H3K79 methylation by DOT1L, and monoubiquitinated H2AK119 stimulates methylation of H3K27 by the PRC2 complex. Recent studies have shed new light on the role of individual subunits and paralogs in regulating the activity of PRC2 and how additional post-translational modifications regulate yeast Dot1 and human DOT1L, as well as provided new insights into the regulation of MLL1 by H2BK120ub.
组蛋白的翻译后修饰在调节转录中起着核心作用。组蛋白 H3 赖氨酸 4（H3K4）和 79（H3K79）的甲基化在激活转录中起作用，而 H3K27 的甲基化是一种抑制标记。这些修饰反过来又依赖于特定组蛋白残基的先前单泛素化，这一现象被称为组蛋白串扰。早期的工作提供了关于单泛素化组蛋白 H2BK120 如何刺激 COMPASS/MLL1 介导的 H3K4 甲基化和 DOT1L 介导的 H3K79 甲基化，以及单泛素化 H2AK119 如何刺激 PRC2 复合物介导的 H3K27 甲基化的机制的深入了解。最近的研究揭示了单个亚基和同源物在调节 PRC2 活性中的作用，以及其他翻译后修饰如何调节酵母 Dot1 和人 DOT1L，以及提供了关于 H2BK120ub 对 MLL1 的调节的新见解。
