Polyubiquitylation of histone H2B
Polyubiquitylation of histone H2B
复制标题
DOI：
10.1091/mbc.e08-01-0050
复制
发表时间：
2008-09-01
影响因子：
3.3
通讯作者：
Tansey, William P.
中科院分区：
文献类型：
--
作者：
Geng, Fuqiang;Tansey, William P.
组蛋白的泛素化共价修饰是一种重要的表观遗传标记，在多种基于染色质的事件中起作用，如组蛋白甲基化、基因沉默和DNA损伤修复。组蛋白泛素化的典型例子是酿酒酵母中的组蛋白H2 B。在这种情况下，泛素与H2 B的赖氨酸123（K123）的连接对于调节活性和转录沉默基因都很重要，并参与组蛋白H3的反式甲基化信号。通常认为H2 B在K123处被单泛素化，并且正是这个单一的泛素部分影响H2 B功能。为了确定这一假设是否正确，我们重新研究了内源性H2 B在酵母中的泛素化状态。我们发现，与预期相反，H2 B是广泛的聚泛素化。H2 B的多泛素化似乎发生在染色质中，与H2 B的破坏无关。H2 B多聚泛素化至少有两种不同的模式：一种发生在K123处，依赖于Rad 6-Bre 1泛素化机制，另一种发生在多个赖氨酸残基上，由未表征的泛素连接酶催化。有趣的是，这些泛素化事件的影响下的不同组合的泛素特异性蛋白酶，这表明它们具有不同的生物功能。这些结果提出了一种可能性，即H2 B泛素化的一些生物学效应是通过泛素链而不是单个泛素基团发挥的。
Covalent modification of histones by ubiquitylation is a prominent epigenetic mark that features in a variety of chromatin-based events such as histone methylation, gene silencing, and repair of DNA damage. The prototypical example of histone ubiquitylation is that of histone H2B in Saccharomyces cerevisiae. In this case, attachment of ubiquitin to lysine 123 (K123) of H2B is important for regulation of both active and transcriptionally silent genes and participates in trans to signal methylation of histone H3. It is generally assumed that H2B is monoubiquitylated at K123 and that it is this single ubiquitin moiety that influences H2B function. To determine whether this assumption is correct, we have re-examined the ubiquitylation status of endogenous H2B in yeast. We find that, contrary to expectations, H2B is extensively polyubiquitylated. Polyubiquitylation of H2B appears to occur within the context of chromatin and is not associated with H2B destruction. There are at least two distinct modes of H2B polyubiquitylation: one that occurs at K123 and depends on the Rad6-Bre1 ubiquitylation machinery and another that occurs on multiple lysine residues and is catalyzed by an uncharacterized ubiquitin ligase(s). Interestingly, these ubiquitylation events are under the influence of different combinations of ubiquitin-specific proteases, suggesting that they have distinct biological functions. These results raise the possibility that some of the biological effects of ubiquitylation of H2B are exerted via ubiquitin chains, rather than a single ubiquitin group.