Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
Biochim Biophys Acta Gene Regul Mech. 2021 Feb;1864(2):194629. doi: 10.1016/j.bbagrm.2020.194629. Epub 2020 Sep 2.
Histone post-translational modifications are essential for the regulation of gene expression in eukaryotes. Gcn5 (KAT2A) is a histone acetyltransferase that catalyzes the post-translational modification at multiple positions of histone H3 through the transfer of acetyl groups to the free amino group of lysine residues. Gcn5 catalyzes histone acetylation in the context of a HAT module containing the Ada2, Ada3 and Sgf29 subunits of the parent megadalton SAGA transcriptional coactivator complex. Biochemical and structural studies have elucidated mechanisms for Gcn5's acetyl- and other acyltransferase activities on histone substrates, for histone H3 phosphorylation and histone H3 methylation crosstalks with histone H3 acetylation, and for how Ada2 increases Gcn5's histone acetyltransferase activity. Other studies have identified Ada2 isoforms in SAGA-related complexes and characterized variant Gcn5 HAT modules containing these Ada2 isoforms. In this review, we highlight biochemical and structural studies of Gcn5 and its functional interactions with Ada2, Ada3 and Sgf29.
组蛋白翻译后修饰对于真核生物中基因表达的调控至关重要。Gcn5（KAT2A）是一种组蛋白乙酰转移酶，通过将乙酰基转移到赖氨酸残基的游离氨基上，催化组蛋白 H3 多个位置的翻译后修饰。Gcn5 在 HAT 模块的背景下催化组蛋白乙酰化，该模块包含亲本兆道尔顿 SAGA 转录共激活复合物的 Ada2、Ada3 和 Sgf29 亚基。生化和结构研究阐明了 Gcn5 在组蛋白底物上的乙酰化和其他酰基转移酶活性、组蛋白 H3 磷酸化以及组蛋白 H3 甲基化与组蛋白 H3 乙酰化的交联、以及 Ada2 如何增加 Gcn5 的组蛋白乙酰转移酶活性的机制。其他研究还在 SAGA 相关复合物中鉴定了 Ada2 同工型，并对包含这些 Ada2 同工型的变体 Gcn5 HAT 模块进行了特征描述。在这篇综述中，我们重点介绍了 Gcn5 的生化和结构研究及其与 Ada2、Ada3 和 Sgf29 的功能相互作用。
