Role of Jade-1 in the Histone Acetyltransferase (HAT) HBO1 Complex
Role of Jade-1 in the Histone Acetyltransferase (HAT) HBO1 Complex
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DOI：
10.1074/jbc.m801407200
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发表时间：
2008-10-24
影响因子：
4.8
通讯作者：
Panchenko, Maria V.
中科院分区：
文献类型：
--
作者：
Foy, Rebecca L.;song, Ihn Young;Panchenko, Maria V.
整体染色质乙酰化的调节对于染色质重塑非常重要。 Jade 蛋白的一个小家族包括 Jade-1L、Jade-2 和 Jade-3，每个都带有两个中分子串联植物同源结构域 (PHD) 锌指。我们之前证明了 Jade-1L 蛋白的短亚型 Jade-1 与内源性组蛋白乙酰转移酶 (HAT) 活性相关。研究发现，Jade-1L/2/3 蛋白与由 HBO1、ING4/5 和 Eaf6 组成的新型 HAT 复合物共纯化。我们研究了 Jade-1/1L 在 HBO1 复合体中的作用。当单独过度表达时，Jade-1/1L 和 HBO1 都不影响组蛋白乙酰化。然而，Jade1/1L 和 HBO1 的共表达以协同方式增加上皮细胞中大部分内源组蛋白 H4 的乙酰化，表明 Jade1/1L 正向调节 HBO1 HAT 活性。相反，小干扰 RNA 介导的内源性 Jade 消耗导致 H4 乙酰化水平降低。此外，体外 Jade-1/1L 的存在使 HBO1 介导的 H4 乙酰化活性增强数倍。 PHD 手指的去除既不影响 Jade-1-HBO1 的结合也不影响 Jade-1-HBO1 的相互稳定，但完全消除了活细胞中和体外重组寡核小体底物中 Jade-1/1L 和 HBO1 介导的组蛋白 H4 乙酰化的协同作用。因此，PHD 对于 Jade-1/1L 诱导的 HBO1 核小体组蛋白乙酰化是必需的。与 Jade-1/1L 相比，PHD 锌指蛋白 ING4/5 未能与 HBO1 协同促进组蛋白乙酰化。 ING4/5 与 HBO1 的物理相互作用发生在 Jade-1L 或 Jade-3 存在的情况下，但不存在 Jade-1 短亚型的情况下。总之，本研究表明 Jade-1/1L 是 HBO1 介导的组蛋白 H4 乙酰化的关键辅助因子。
Regulation of global chromatin acetylation is important for chromatin remodeling. A small family of Jade proteins includes Jade-1L, Jade-2, and Jade-3, each bearing two mid-molecule tandem plant homology domain (PHD) zinc fingers. We previously demonstrated that the short isoform of Jade-1L protein, Jade-1, is associated with endogenous histone acetyltransferase (HAT) activity. It has been found that Jade-1L/2/3 proteins co-purify with a novel HAT complex, consisting of HBO1, ING4/5, and Eaf6. We investigated a role for Jade-1/1L in the HBO1 complex. When overexpressed individually, neither Jade-1/1L nor HBO1 affected histone acetylation. However, co-expression of Jade1/1L and HBO1 increased acetylation of the bulk of endogenous histone H4 in epithelial cells in a synergistic manner, suggesting that Jade1/1L positively regulates HBO1 HAT activity. Conversely, small interfering RNA-mediated depletion of endogenous Jade resulted in reduced levels of H4 acetylation. Moreover, HBO1-mediated H4 acetylation activity was enhanced severalfold by the presence of Jade-1/1L in vitro. The removal of PHD fingers affected neither binding nor mutual Jade-1-HBO1 stabilization but completely abrogated the synergistic Jade-1/1L- and HBO1-mediated histone H4 acetylation in live cells and in vitro with reconstituted oligonucleosome substrates. Therefore, PHDs are necessary for Jade-1/1L- induced acetylation of nucleosomal histones by HBO1. In contrast to Jade-1/1L, the PHD zinc finger protein ING4/5 failed to synergize with HBO1 to promote histone acetylation. The physical interaction of ING4/5 with HBO1 occurred in the presence of Jade-1L or Jade-3 but not with the Jade-1 short isoform. In summary, this study demonstrates that Jade-1/1L are crucial co-factors for HBO1-mediated histone H4 acetylation.