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The Double-Histone-Acetyltransferase Complex ATAC Is Essential for Mammalian Development

机译:双组蛋白-乙酰转移酶复合物ATAC对哺乳动物的发育至关重要

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Acetylation of the histone tails, catalyzed by histone acetyltransferases (HATs), is a well-studied process that contributes to transcriptionally active chromatin states. Here we report the characterization of a novel mammalian HAT complex, which contains the two acetyltransferases GCN5 and ATAC2 as well as other proteins linked to chromatin metabolism. This multisubunit complex has a similar but distinct subunit composition to that of the Drosophila ADA2A-containing complex (ATAC). Recombinant ATAC2 has a weak HAT activity directed to histone H4. Moreover, depletion of ATAC2 results in the disassembly of the complex, indicating that ATAC2 not only carries out an enzymatic function but also plays an architectural role in the stability of mammalian ATAC. By targeted disruption of the Atac2 locus in mice, we demonstrate for the first time the essential role of the ATAC complex in mammalian development, histone acetylation, cell cycle progression, and prevention of apoptosis during embryogenesis.
机译:由组蛋白乙酰转移酶(HATs)催化的组蛋白尾巴的乙酰化是一个经过充分研究的过程,可促进转录活性染色质的状态。在这里,我们报告了一种新型哺乳动物HAT复合物的表征,该复合物包含两个乙酰基转移酶GCN5和ATAC2以及与染色质代谢相关的其他蛋白质。该多亚基复合物具有与含果蝇 ADA2A的复合物(ATAC)类似但不同的亚基组成。重组ATAC2具有针对组蛋白H4的弱HAT活性。此外,ATAC2的消耗会导致复合物的分解,这表明ATAC2不仅具有酶促功能,而且在哺乳动物ATAC的稳定性中也起着建筑作用。通过有针对性地破坏小鼠中的 Atac2 基因座,我们首次证明了ATAC复合物在哺乳动物发育,组蛋白乙酰化,细胞周期进程和防止胚胎发生过程中的凋亡中的重要作用。

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