The human nucleosome acetyltransferase of histone H4 (NuA4)/Tat-interactive protein, 60 kilodalton (TIP60) coactivator complex, a fusion of the yeast switch/sucrose nonfermentable related 1 (SWR1) and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4, H2A, and H2A.Z to regulate gene expression and maintain genome stability. Our cryo–electron microscopy studies show that, within the NuA4/TIP60 complex, the E1A binding protein P400 (EP400) subunit serves as a scaffold holding the different functional modules in specific positions, creating a distinct arrangement of the actin-related protein (ARP) module. EP400 interacts with the transformation/transcription domain-associated protein (TRRAP) subunit by using a footprint that overlaps with that of the Spt-Ada-Gcn5 acetyltransferase (SAGA) 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.

中文翻译：

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人类 NuA4/TIP60 乙酰转移酶和染色质重塑复合物的结构见解


人类核小体组蛋白乙酰转移酶 H4 (NuA4)/Tat 相互作用蛋白、60 kilodalton (TIP60) 共激活剂复合物、酵母开关/蔗糖不可发酵相关 1 (SWR1) 和 NuA4 复合物的融合体，均包含组蛋白变体 H2A.Z进入核小体并乙酰化组蛋白 H4、H2A 和 H2A.Z，以调节基因表达并维持基因组稳定性。我们的冷冻电子显微镜研究表明，在 NuA4/TIP60 复合物中，E1A 结合蛋白 P400 (EP400) 亚基充当支架，将不同的功能模块固定在特定位置，从而形成肌动蛋白相关蛋白 (ARP) 的独特排列。 ） 模块。 EP400 通过使用与 Spt-Ada-Gcn5 乙酰转移酶 (SAGA) 复合物重叠的足迹与转化/转录域相关蛋白 (TRRAP) 亚基相互作用，从而防止杂合复合物的形成。 TRRAP 亚基的丢失导致 NuA4/TIP60 错误定位，导致 H2A.Z 及其乙酰化在基因组中重新分布，强调了 NuA4/TIP60 作为单个大分子组装体的双重功能。