The SAGA coactivator complex acts on the whole transcribed genome and is required for RNA polymerase II transcription.
The SAGA coactivator complex acts on the whole transcribed genome and is required for RNA polymerase II transcription.
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DOI：
10.1101/gad.250225.114
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发表时间：
2014-09-15
影响因子：
10.5
通讯作者：
Devys D
中科院分区：
文献类型：
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作者：
Bonnet J;Wang CY;Baptista T;Vincent SD;Hsiao WC;Stierle M;Kao CF;Tora L;Devys D
佐贺辅激活因子复合物含有不同的染色质修饰活性，并被DNA结合的激活因子募集以调节基因子集的表达。Bonnet等人发现佐贺使启动子乙酰化并使所有表达基因的转录区域去泛素化。佐贺还在所有表达基因的RNA聚合酶II募集中起关键作用。这项研究揭示了佐贺作为所有RNA聚合酶II转录的真正辅因子的新功能。佐贺（Spt-Ada-Gcn 5乙酰转移酶）共激活因子复合物含有不同的染色质修饰活性，并被DNA结合的激活因子募集以调节基因子集的表达。令人惊讶的是，最近的研究揭示了全基因组SAGA结合谱与复合物亚基耗尽后基因表达的变化之间几乎没有重叠。作为染色质上佐贺募集的指标，我们在酵母和人类细胞中监测组蛋白H3 K9乙酰化和H2 B泛素化的全基因组分布，其分别被佐贺沉积或去除。这些修改后的相应的酶失活的变化表明，佐贺乙酰化的启动子和deubiquitinates所有表达的基因的转录区域。与这种广泛的分布一致，我们发现佐贺在所有表达基因的RNA聚合酶II招募中起着关键作用。此外，通过定量新合成的RNA，我们证明了佐贺失活诱导所有测试基因的mRNA合成的强烈减少。佐贺去泛素化活性的分析进一步揭示了佐贺以非常快的方式作用于整个转录的基因组，表明复合物与染色质的高度动态关联。因此，我们的研究揭示了佐贺作为所有RNA聚合酶II转录的真正辅因子的新功能。
The SAGA coactivator complex contains distinct chromatin-modifying activities and is recruited by DNA-bound activators to regulate the expression of a subset of genes. Bonnet et al. discovered that SAGA acetylates the promoters and deubiquitinates the transcribed region of all expressed genes. SAGA also plays a critical role for RNA polymerase II recruitment at all expressed genes. This study uncovers a new function for SAGA as a bona fide cofactor for all RNA polymerase II transcription. The SAGA (Spt–Ada–Gcn5 acetyltransferase) coactivator complex contains distinct chromatin-modifying activities and is recruited by DNA-bound activators to regulate the expression of a subset of genes. Surprisingly, recent studies revealed little overlap between genome-wide SAGA-binding profiles and changes in gene expression upon depletion of subunits of the complex. As indicators of SAGA recruitment on chromatin, we monitored in yeast and human cells the genome-wide distribution of histone H3K9 acetylation and H2B ubiquitination, which are respectively deposited or removed by SAGA. Changes in these modifications after inactivation of the corresponding enzyme revealed that SAGA acetylates the promoters and deubiquitinates the transcribed region of all expressed genes. In agreement with this broad distribution, we show that SAGA plays a critical role for RNA polymerase II recruitment at all expressed genes. In addition, through quantification of newly synthesized RNA, we demonstrated that SAGA inactivation induced a strong decrease of mRNA synthesis at all tested genes. Analysis of the SAGA deubiquitination activity further revealed that SAGA acts on the whole transcribed genome in a very fast manner, indicating a highly dynamic association of the complex with chromatin. Thus, our study uncovers a new function for SAGA as a bone fide cofactor for all RNA polymerase II transcription.
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