Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase
Identification and characterization of a novel human histone H3 lysine 36-specific methyltransferase
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DOI：
10.1074/jbc.m504012200
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发表时间：
2005-10-21
影响因子：
4.8
通讯作者：
Chen, Z
中科院分区：
文献类型：
--
作者：
Sun, XJ;Wei, J;Chen, Z
组蛋白甲基化在真核生物的转录调控中起着重要的作用。许多具有不同功能的组蛋白甲基转移酶（HMTases）已被鉴定。HSPC 069/HYPB基因最初是从人类造血干/祖细胞（HSPC）中分离的，并且其也被鉴定为亨廷顿蛋白相互作用蛋白，与亨廷顿病（HD）的发病机制有关。然而，其生物化学功能知之甚少。在这里，我们报告的亨廷顿蛋白相互作用蛋白B（HYPB）的结构和功能特性。1)三重AWS-SET-PostSET结构域介导组蛋白H3赖氨酸36特异性HMTase活性。2)富含谷氨酰胺和脯氨酸的低电荷区域已被表征为新的转录激活结构域。该区域的结构特征在脊椎动物中是进化上保守的。3)免疫共沉淀试验表明，HYPB蛋白与过度磷酸化的RNA聚合酶II（RNAPII），但不是非磷酸化的形式。此外，HYPB蛋白的RNAPII相关区域已被鉴定为包括C-末端142个氨基酸。因此，我们的研究结果表明，HYPB HMTase可能协调组蛋白甲基化和转录调控在哺乳动物和开放的前景，进一步研究HYPB蛋白在造血和HD的发病机制的潜在作用。
Histone methylation plays an important role in eukaryotic transcriptional regulation. A number of histone methyltransferases (HMTases) with distinct functions have been identified. The HSPC069/HYPB gene was originally isolated from the human hematopoietic stem/progenitor cells (HSPCs), and it was also identified as a huntingtin interacting protein, implicated in the pathogenesis of Huntington disease (HD). However, its biochemical function is poorly understood. Here we report the structural and functional characterization of the huntingtin interacting protein B (HYPB). 1) The triplicate AWS-SET-PostSET domains mediate a histone H3 lysine 36 specific HMTase activity. 2) A low charged region that is rich in glutamine and proline has been characterized as a novel transcriptional activation domain. The structural features of this region are evolutionarily conserved in vertebrates. 3) Coimmunoprecipitation assays indicate that HYPB protein associates with hyperphosphorylated RNA polymerase II (RNAPII) but not the unphosphorylated form. Furthermore, the RNAPII-association region of HYPB protein has been identified to encompass the C-terminal 142 amino acids. Thus, our results suggest that HYPB HMTase may coordinate histone methylation and transcriptional regulation in mammals and open perspective for the further study of the potential roles of HYPB protein in hematopoiesis and pathogenesis of HD.