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首页> 外文期刊>Journal of Molecular Biology >Tandem PHD aingers of MORF/MOZ acetyltransferases display selectivity for acetylated histone H3 and are required for the association with chromatin
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Tandem PHD aingers of MORF/MOZ acetyltransferases display selectivity for acetylated histone H3 and are required for the association with chromatin

机译：MORF / MOZ乙酰基转移酶的串联PHD前体显示出对乙酰化组蛋白H3的选择性，是与染色质结合所必需的

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摘要

MORF [MOZ (monocytic leukemia zinc-finger protein)-related factor] and MOZ are catalytic subunits of histone acetyltransferase (HAT) complexes essential in hematopoiesis, neurogenesis, skeletogenesis and other developmental programs and implicated in human leukemias. The canonical HAT domain of MORF/MOZ is preceded by a tandem of plant homeodomain (PHD) fingers whose biological roles and requirements for MORF/MOZ activity are unknown. Here, we demonstrate that the tandem PHD1/2 fingers of MORF recognize the N-terminal tail of histone H3. Acetylation of Lys9 (H3K9ac) or Lys14 (H3K14ac) enhances binding of MORF PHD1/2 to unmodified H3 peptides twofold to threefold. The selectivity for acetylated H3 tail is conserved in the double PHD1/2 fingers of MOZ. This interaction requires the intact N-terminus of histone H3 and is inhibited by trimethylation of Lys4. Biochemical analysis using NMR, fluorescence spectroscopy and mutagenesis identified key amino acids of MORF PHD1/2 necessary for the interaction with histones. Fluorescence microscopy and immunoprecipitation experiments reveal that both PHD fingers are required for binding to H3K14ac in vivo and localization to chromatin. The HAT assays indicate that the interaction with H3K14ac may promote enzymatic activity in trans. Together, our data suggest that the PHD1/2 fingers play a role in MOZ/MORF HATs association with the chromatic regions enriched in acetylated marks.
机译：MORF [MOZ（单核细胞白血病锌指蛋白）相关因子]和MOZ是组蛋白乙酰转移酶（HAT）复合物的催化亚基，在血细胞生成，神经发生，骨骼生成和其他发育程序中必不可少，并与人类白血病有关。 MORF / MOZ的规范HAT域之前是一串串联的植物同源域（PHD）手指，其生物学作用和对MORF / MOZ活性的要求尚不清楚。在这里，我们证明了MORF的串联PHD1 / 2手指识别出组蛋白H3的N末端尾巴。 Lys9（H3K9ac）或Lys14（H3K14ac）的乙酰化可将MORF PHD1 / 2与未修饰的H3肽的结合力提高两倍至三倍。在MOZ的双PHD1 / 2指中保留了乙酰化H3尾巴的选择性。这种相互作用需要完整的组蛋白H3 N端，并被Lys4的三甲基化抑制。使用NMR，荧光光谱和诱变的生化分析确定了与组蛋白相互作用所必需的MORF PHD1 / 2的关键氨基酸。荧光显微镜和免疫沉淀实验表明，在体内结合H3K14ac和定位于染色质均需要两个PHD指。 HAT分析表明与H3K14ac的相互作用可能促进反式酶的活性。在一起，我们的数据表明，PHD1 / 2手指在MOZ / MORF HATs与富含乙酰化标记的色域相关的过程中发挥了作用。

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