Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
J Biol Chem. 2021 Aug;297(2):100939. doi: 10.1016/j.jbc.2021.100939. Epub 2021 Jul 3.
Histone lysine methylation is a key epigenetic modification that regulates eukaryotic transcription. Here, we comprehensively review the function and regulation of the histone methylation network in the budding yeast and model eukaryote, Saccharomyces cerevisiae. First, we outline the lysine methylation sites that are found on histone proteins in yeast (H3K4me1/2/3, H3K36me1/2/3, H3K79me1/2/3, and H4K5/8/12me1) and discuss their biological and cellular roles. Next, we detail the reduced but evolutionarily conserved suite of methyltransferase (Set1p, Set2p, Dot1p, and Set5p) and demethylase (Jhd1p, Jhd2p, Rph1p, and Gis1p) enzymes that are known to control histone lysine methylation in budding yeast cells. Specifically, we illustrate the domain architecture of the methylation enzymes and highlight the structural features that are required for their respective functions and molecular interactions. Finally, we discuss the prevalence of post-translational modifications on yeast histone methylation enzymes and how phosphorylation, acetylation, and ubiquitination in particular are emerging as key regulators of enzyme function. We note that it will be possible to completely connect the histone methylation network to the cell's signaling system, given that all methylation sites and cognate enzymes are known, most phosphosites on the enzymes are known, and the mapping of kinases to phosphosites is tractable owing to the modest set of protein kinases in yeast. Moving forward, we expect that the rich variety of post-translational modifications that decorates the histone methylation machinery will explain many of the unresolved questions surrounding the function and dynamics of this intricate epigenetic network.
组蛋白赖氨酸甲基化是一种关键的表观遗传修饰，调节真核转录。在这里，我们全面回顾了芽殖酵母和模式真核生物酿酒酵母中组蛋白甲基化网络的功能和调控。首先，我们概述了在酵母中发现的组蛋白上的赖氨酸甲基化位点（H3K4me1/2/3、H3K36me1/2/3、H3K79me1/2/3 和 H4K5/8/12me1），并讨论了它们的生物学和细胞作用。接下来，我们详细介绍了一套数量减少但进化上保守的甲基转移酶（Set1p、Set2p、Dot1p 和 Set5p）和去甲基酶（Jhd1p、Jhd2p、Rph1p 和 Gis1p），这些酶已知可以控制芽殖酵母细胞中的组蛋白赖氨酸甲基化。具体来说，我们说明了甲基化酶的结构域架构，并强调了对其各自功能和分子相互作用所必需的结构特征。最后，我们讨论了酵母组蛋白甲基化酶上的翻译后修饰的普遍性，以及磷酸化、乙酰化和泛素化如何特别成为酶功能的关键调节剂。我们注意到，鉴于所有的甲基化位点和同源酶都是已知的，大多数酶上的磷酸化位点是已知的，并且由于酵母中蛋白激酶的数量适中，激酶到磷酸化位点的映射是可行的，因此有可能将组蛋白甲基化网络完全连接到细胞的信号系统。展望未来，我们预计修饰组蛋白甲基化机器的丰富的翻译后修饰将解释围绕这个复杂的表观遗传网络的功能和动态的许多未解决的问题。
