Department of Biochemistry and Biophysics, 120 Mason Farm Rd, University of North Carolina at Chapel Hill, NC 27599, USA.
Department of Biochemistry and Purdue University Center for Cancer Research, Purdue University, Hansen Life Science Research Building, 201S, University Street, West Lafayette, IN 47907; USA.
Biochim Biophys Acta Gene Regul Mech. 2021 Feb;1864(2):194600. doi: 10.1016/j.bbagrm.2020.194600. Epub 2020 Jul 6.
Fueled by key technological innovations during the last several decades, chromatin-based research has greatly advanced our mechanistic understanding of how genes are regulated by epigenetic factors and their associated histone-modifying activities. Most notably, the landmark finding that linked histone acetylation by Gcn5 of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex to gene activation ushered in a new area of chromatin research and a realization that histone-modifying activities have integral genome functions. This review will discuss past and recent studies that have shaped our understanding of how the histone-modifying activities of SAGA are regulated by, and modulate the outcomes of, other histone modifications during gene transcription. Because much of our understanding of SAGA was established with budding yeast, we will focus on yeast as a model. We discuss the actions of cis- and trans-histone crosstalk pathways that involve the histone acetyltransferase, deubiquitylase, and reader domains of SAGA. We conclude by considering unanswered questions about SAGA and related complexes.
在过去几十年的关键技术创新的推动下，基于染色质的研究极大地促进了我们对基因如何被表观遗传因子及其相关组蛋白修饰活性调控的机制理解。最值得注意的是，一个里程碑式的发现将 Spt-Ada-Gcn5-acetyltransferase (SAGA) 复合物的 Gcn5 介导的组蛋白乙酰化与基因激活联系起来，开创了染色质研究的一个新领域，并认识到组蛋白修饰活性具有完整的基因组功能。本综述将讨论过去和最近的研究，这些研究塑造了我们对 SAGA 的组蛋白修饰活性如何被其他组蛋白修饰调控，并调节基因转录过程中的结果的理解。由于我们对 SAGA 的理解大部分是在 budding yeast 中建立的，我们将重点讨论酵母作为模型。我们讨论了 cis-和 trans-组蛋白串扰途径的作用，涉及 SAGA 的组蛋白乙酰转移酶、去泛素化酶和阅读器结构域。最后，我们考虑了关于 SAGA 和相关复合物的未解决问题。
