Wahab Suzanne, Saettone Alejandro, Nabeel-Shah Syed, Dannah Nora, Fillingham Jeffrey
Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada.
Front Cell Dev Biol. 2020 Jun 30;8:509. doi: 10.3389/fcell.2020.00509. eCollection 2020.
The eukaryotic histone acetylation cycle is composed of three classes of proteins, histone acetyltransferases (HATs) that add acetyl groups to lysine amino acids, bromodomain (BRD) containing proteins that are one of the most characterized of several protein domains that recognize acetyl-lysine (Kac) and effect downstream function, and histone deacetylases (HDACs) that catalyze the reverse reaction. Dysfunction of selected proteins of these three classes is associated with human disease such as cancer. Additionally, the HATs, BRDs, and HDACs of fungi and parasitic protozoa present potential drug targets. Despite their importance, the function and mechanisms of HATs, BRDs, and HDACs and how they relate to chromatin remodeling (CR) remain incompletely understood. (Tt) provides a highly tractable single-celled free-living protozoan model for studying histone acetylation, featuring a massively acetylated somatic genome, a property that was exploited in the identification of the first nuclear/type A HAT Gcn5 in the 1990s. Since then, remains an under-explored model for the molecular analysis of HATs, BRDs, and HDACs. Studies of HATs, BRDs, and HDACs in have the potential to reveal the function of HATs and BRDs relevant to both fundamental eukaryotic biology and to the study of disease mechanisms in parasitic protozoa.
组蛋白乙酰转移酶（HATs），其将乙酰基添加到赖氨酸氨基酸上；含溴结构域（BRD）的蛋白质，它是识别乙酰赖氨酸（Kac）并影响下游功能的几个蛋白质结构域中研究得最为透彻的结构域之一；以及催化逆反应的组蛋白脱乙酰酶（HDACs）。这三类中某些蛋白质的功能障碍与癌症等人类疾病相关。此外，真菌和寄生原生动物的HATs、BRDs和HDACs是潜在的药物靶点。尽管它们很重要，但HATs、BRDs和HDACs 的功能和机制以及它们与染色质重塑（CR）的关系仍未完全了解。（某生物）为研究组蛋白乙酰化提供了一个易于处理的单细胞自由生活原生动物模型，其具有大量乙酰化的体细胞基因组，这一特性在20世纪90年代首次鉴定核/ A型HAT Gcn5时得到了利用。从那时起，（某生物）仍然是一个未被充分探索的用于HATs、BRDs和HDACs分子分析的模型。对（某生物）中HATs、BRDs和HDACs的研究有可能揭示与基础真核生物学以及寄生原生动物疾病机制研究相关的HATs和BRDs的功能。
