Recognition of Unmodified Histone H3 by the First PHD Finger of Bromodomain-PHD Finger Protein 2 Provides Insights into the Regulation of Histone Acetyltransferases Monocytic Leukemic Zinc-finger Protein (MOZ) and MOZ-related factor (MORF)
Recognition of Unmodified Histone H3 by the First PHD Finger of Bromodomain-PHD Finger Protein 2 Provides Insights into the Regulation of Histone Acetyltransferases Monocytic Leukemic Zinc-finger Protein (MOZ) and MOZ-related factor (MORF)
复制标题
溴结构域-PHD 指蛋白 2 的第一个 PHD 指对未修饰的组蛋白 H3 的识别提供了对组蛋白乙酰转移酶、单核细胞白血病锌指蛋白 (MOZ) 和 MOZ 相关因子 (MORF) 调节的深入了解
DOI：
10.1074/jbc.m111.244400
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发表时间：
2011-10-21
影响因子：
4.8
通讯作者：
Shi, Yunyu
中科院分区：
文献类型：
--
作者：
Qin, Su;Jin, Lei;Shi, Yunyu
MOZ（单核细胞白血病锌指蛋白）和MORF（MOZ相关因子）是HOX基因表达以及胚胎和出生后发育的重要组蛋白乙酰转移酶。它们通过支架蛋白BRPF 1/2/3（溴结构域-PHD（植物同源结构域）指蛋白1、2或3）与其他调节亚基形成复合物。BRPF蛋白具有多个结构域，包括两个PHD指，用于与组蛋白的潜在相互作用。在这里，我们表明，BRPF 2的第一个PHD指特异性地识别未修饰的组蛋白H3（unH 3）的N-末端尾部，并报告了该PHD指的溶液结构，包括游离的和与unH 3肽复合的。结构分析显示，unH 3肽形成第三个反平行β链，与PHD 1双链反平行β折叠配对。结合特异性主要是通过识别精氨酸2和赖氨酸4的unH 3的保守的天冬氨酸PHD 1和苏氨酸6的unH 3的保守的天冬酰胺。等温滴定量热法和NMR分析表明，翻译后修饰，如H3 R2 me 2as，H3 T3 ph，H3 K4 me，H3 K4 ac和H3 T6 ph拮抗组蛋白H3和PHD 1之间的相互作用。此外，组蛋白结合的PHD 1是重要的BRPF 2本地化的HOXA 9基因座在体内。PHD 1在酵母NuA 3和其他组蛋白乙酰转移酶复合物中高度保守，因此本文报道的结果也揭示了这些复合物的功能和调节。
MOZ (monocytic leukemic zinc-finger protein) and MORF (MOZ-related factor) are histone acetyltransferases important for HOX gene expression as well as embryo and postnatal development. They form complexes with other regulatory subunits through the scaffold proteins BRPF1/2/3 (bromodomain-PHD (plant homeodomain) finger proteins 1, 2, or 3). BRPF proteins have multiple domains, including two PHD fingers, for potential interactions with histones. Here we show that the first PHD finger of BRPF2 specifically recognizes the N-terminal tail of unmodified histone H3 (unH3) and report the solution structures of this PHD finger both free and in complex with the unH3 peptide. Structural analysis revealed that the unH3 peptide forms a third antiparallel beta-strand that pairs with the PHD1 two-stranded antiparallel beta-sheet. The binding specificity was determined primarily through the recognition of arginine 2 and lysine 4 of the unH3 by conserved aspartic acids of PHD1 and of threonine 6 of the unH3 by a conserved asparagine. Isothermal titration calorimetry and NMR assays showed that post-translational modifications such as H3R2me2as, H3T3ph, H3K4me, H3K4ac, and H3T6ph antagonized the interaction between histone H3 and PHD1. Furthermore, histone binding by PHD1 was important for BRPF2 to localize to the HOXA9 locus in vivo. PHD1 is highly conserved in yeast NuA3 and other histone acetyltransferase complexes, so the results reported here also shed light on the function and regulation of these complexes.