Evidence for the existence of an HP1-mediated subcode within the histone code
Evidence for the existence of an HP1-mediated subcode within the histone code
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DOI：
10.1038/ncb1383
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发表时间：
2006-04-01
影响因子：
21.3
通讯作者：
Urrutia, R
中科院分区：
文献类型：
--
作者：
Lomberk, G;Bensi, D;Urrutia, R
目前，哺乳动物异色蛋白HP1 α， HP1 β和泛核HP1 γ。被认为是甲基k9 - h3介导沉默的“守门人”。了解这些蛋白与翻译后修饰组蛋白的结合是如何开启和关闭的，将进一步了解组蛋白编码是如何被调节的。在这里，我们报道了所有三种HP1亚型都可以被广泛修饰，类似于组蛋白，这表明基因表达的沉默可能在组蛋白代码之外进一步调节。为了评估这些修饰的潜在影响，我们分析了HP1 γ在Ser 83的磷酸化作为“模型修饰”。我们证明P-Ser 83-HP1 γ具有完全的常染色质定位，与Ku70（一种参与多核过程的调节蛋白）相互作用，具有受损的沉默活性，并作为转录伸长的标记。这些观察结果预测，甲基- k9 - h3通过修饰哺乳动物HP1蛋白对沉默的调节可能比以前认为的更复杂，并表明HP1介导的“沉默亚码”的存在是组蛋白编码指令的基础。
Currently, the mammalian heterochromatic proteins HP1 alpha, HP1 beta and the pan-nuclear HP1 gamma. are considered 'gatekeepers' of methyl-K9-H3-mediated silencing. Understanding how the binding of these proteins to post-translationally modified histones is switched on and off will further our knowledge of how the histone code is modulated. Here, we report that all three HP1 isoforms can be extensively modified, similar to histones, suggesting that the silencing of gene expression may be further regulated beyond the histone code. To assess the potential impact of these modifications, we analysed the phosphorylation of HP1 gamma at Ser 83 as a 'model modification'. We demonstrate that P-Ser 83-HP1 gamma has an exclusively euchromatic localization, interacts with Ku70 ( a regulatory protein involved in multiple nuclear procesess), has impaired silencing activity and serves as a marker for transcription elongation. These observations predict that regulation of silencing by methyl-K9-H3 through modification of mammalian HP1 proteins may be more complex than previously thought and suggests the existence of an HP1-mediated 'silencing subcode' that underlies the instructions of the histone code.