The ZFP-1(AF10)/DOT-1 complex opposes H2B ubiquitination to reduce Pol II transcription.

The ZFP-1(AF10)/DOT-1 complex opposes H2B ubiquitination to reduce Pol II transcription.
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DOI:
10.1016/j.molcel.2013.06.002
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发表时间:
2013-06-27
期刊:
影响因子:
16
通讯作者:
Grishok, Alla
Grishok, Alla
中科院分区:
生物学1区
文献类型:
--
作者:
Cecere, Germano;Hoersch, Sebastian;Jensen, Morten B.;Dixit, Shiv;Grishok, Alla

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在包括秀丽隐杆线虫在内的后生动物中,转录延伸的抑制在基因调控中起着重要作用。在这里,我们结合基因组和生化方法来剖析ZFP-1,秀丽隐杆线虫AF10同源物,在转录控制中的作用。我们发现ZFP-1及其相互作用的伙伴DOT-1.1在广泛表达的重要基因上负调控聚合酶II (Pol II)转录水平具有全局作用。此外,ZFP-1/DOT-1.1复合体有助于在发育过程中必需基因上的Pol II进行性暂停,以及在应激反应中Pol II快速暂停。ZFP-1/DOT-1.1对Pol II转录的减缓与H3K79甲基化的增加和H2B单泛素化的减少有关,从而促进转录。我们提出了一个模型,其中ZFP-1/DOT-1.1的募集和H3K79甲基化沉积在高表达基因上启动了一个调节其表达的负反馈机制。
The inhibition of transcriptional elongation plays an important role in gene regulation in metazoans, including C. elegans. Here, we combine genomic and biochemical approaches to dissect a role of ZFP-1, the C. elegans AF10 homolog, in transcriptional control. We show that ZFP-1 and its interacting partner DOT-1.1 have a global role in negatively modulating the level of polymerase II (Pol II) transcription on essential widely expressed genes. Moreover, the ZFP-1/DOT-1.1 complex contributes to progressive Pol II pausing on essential genes during development and to rapid Pol II pausing during stress response. The slowing down of Pol II transcription by ZFP-1/DOT-1.1 is associated with an increase in H3K79 methylation and a decrease in H2B monoubiquitination, which promotes transcription. We propose a model wherein the recruitment of ZFP-1/DOT-1.1 and deposition of H3K79 methylation at highly expressed genes initiates a negative feedback mechanism for the modulation of their expression.
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