Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription
Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription
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DOI：
10.1074/jbc.c300494200
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发表时间：
2004-01-16
影响因子：
4.8
通讯作者：
Grant, PA
中科院分区：
文献类型：
--
作者：
Daniel, JA;Torok, MS;Grant, PA
真核细胞染色质组蛋白成分的翻译后修饰在染色质结构和基因表达的调节中起着重要作用(1)。鉴于依赖Rad6/Bre1的组蛋白H_2B泛素化对H3二甲基化(在赖氨酸4和79)和基因沉默(2-7)的要求，从H_2B中去除泛素可能对转录有显著的调节作用。在这里，我们发现了一个假定的脱泛素化酶Ubp8，它是酵母中SPT-Ada-Gcn5-乙酰转移酶(SAGA)和类似SAGA(SLIK)组蛋白乙酰转移酶(HAT)复合体的非必需成分。该基因的破坏显著增加了泛素化的-H_2B的细胞水平，SAGA和SLIK被证明具有H_2B脱泛素酶的活性。这些发现第一次展示了如何以一种受调控的方式从组蛋白H2B中去除泛素部分。Ubp8是SAGA和SLIK依赖基因GAL10充分表达所必需的，在激活条件下被招募到该基因的上游激活序列(UAS)，而Rad6则解离。此外，在激活条件下，UAS中赖氨酸4上H3的三甲基化显著增加，值得注意的是，Ubp8被证明在调节该残基的甲基化状态中具有作用。总而言之，这些数据表明，SAGA和SLIK HAT复合体可以调节一系列综合的组蛋白修饰，抵消改变染色质和调节基因表达的抑制效应。
Post-translational modifications of the histone protein components of eukaryotic chromatin play an important role in the regulation of chromatin structure and gene expression ( 1). Given the requirement of Rad6/Bre1-dependent ubiquitination of histone H2B for H3 dimethylation (at lysines 4 and 79) and gene silencing (2 - 7), removal of ubiquitin from H2B may have a significant regulatory effect on transcription. Here we show that a putative deubiquitinating enzyme, Ubp8, is a structurally nonessential component of both the Spt-Ada-Gcn5-acetyltransferase ( SAGA) and SAGA-like (SLIK) histone acetyltransferase ( HAT) complexes in yeast. Disruption of this gene dramatically increases the cellular level of ubiquitinated-H2B, and SAGA and SLIK are shown to have H2B deubiquitinase activity. These findings demonstrate, for the first time, how the ubiquitin moiety can be removed from histone H2B in a regulated fashion. Ubp8 is required for full expression of the SAGA- and SLIK-dependent gene GAL10 and is recruited to the upstream activation sequence (UAS) of this gene under activating conditions, while Rad6 dissociates. Furthermore, trimethylation of H3 at lysine 4 within the UAS increases significantly under activating conditions, and remarkably, Ubp8 is shown to have a role in regulating the methylation status of this residue. Collectively, these data suggest that the SAGA and SLIK HAT complexes can regulate an integrated set of multiple histone modifications, counteracting repressive effects that alter chromatin and regulate gene expression.