美国加州大学Eva Nogales和加拿大拉瓦尔大学癌症研究中心Jacques Côté共同合作，近期取得重要工作进展。他们研究分析了人类NuA4/TIP60乙酰转移酶和染色质重塑复合体的结构。相关研究成果2024年8月1日在线发表于《科学》杂志上。

据介绍，人类NuA4/TIP60共激活物复合物是酵母SWR1和NuA4复合物的融合物，两者都含有组蛋白变体H2A.Z转化为核小体和乙酰化组蛋白H4/H2A/H2A.Z调节基因表达并维持基因组稳定性。

冷冻电镜研究表明，在NuA4/TIP60复合物中，EP400亚基充当支架，将不同的功能模块固定在特定位置，从而形成ARP模块的独特排列。EP400使用与SAGA乙酰转移酶复合物重叠的足迹与TRRAP亚基相互作用，防止形成杂合复合物。TRRAP亚基的缺失会导致NuA4/TIP60的定位错误，从而导致H2A.Z的重新分布及其在整个基因组中的乙酰化，强调了NuA4/TIP60作为单个大分子组装体的双重功能。

附：英文原文

Title: Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex

Author: Zhenlin Yang, Amel Mameri, Claudia Cattoglio, Catherine Lachance, Alfredo Jose Florez Ariza, Jie Luo, Jonathan Humbert, Deepthi Sudarshan, Arul Banerjea, Maxime Galloy, Amélie Fradet-Turcotte, Jean-Philippe Lambert, Jeff A. Ranish, Jacques Cté, Eva Nogales

Issue&Volume: 2024-08-01

Abstract: The human NuA4/TIP60 co-activator complex, a fusion of the yeast SWR1 and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4/H2A/H2A.Z to regulate gene expression and maintain genome stability. Our cryo-electron microscopy studies show that, within the NuA4/TIP60 complex, the EP400 subunit serves as a scaffold holding the different functional modules in specific positions, creating a unique arrangement of the ARP module. EP400 interacts with the TRRAP subunit using a footprint that overlaps with that of the SAGA acetyltransferase complex, preventing the formation of a hybrid complex. Loss of the TRRAP subunit leads to mislocalization of NuA4/TIP60, resulting in the redistribution of H2A.Z and its acetylation across the genome, emphasizing the dual functionality of NuA4/TIP60 as a single macromolecular assembly.

DOI: adl5816

Source: https://www.science.org/doi/10.1126/science.adl5816