The Neurospora RNA polymerase II kinase CTK negatively regulates catalase expression in a chromatin context-dependent manner
The Neurospora RNA polymerase II kinase CTK negatively regulates catalase expression in a chromatin context-dependent manner
复制标题
脉孢菌 RNA 聚合酶 II 激酶 CTK 以染色质背景依赖性方式负向调节过氧化氢酶表达
DOI：
10.1111/1462-2920.14821
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发表时间：
2019-10-21
影响因子：
5.1
通讯作者：
He, Qun
中科院分区：
文献类型：
--
作者：
Duan, Jiabin;Liu, Qingqing;He, Qun
清除和适应活性氧（ROS）是细胞生存的关键。与其他真核生物一样，脉孢菌过氧化氢酶是负责ROS清除的主要酶，其表达受到生长和环境条件的严格调控。RNA聚合酶II羧基末端结构域（RNAPII CTD）激酶复合物（CTK复合物）通过在转录起始位点附近释放暂停的RNAPII并促进转录延伸而被称为许多诱导型基因的正延伸因子。然而，在这里，我们表明，CTK复合物组件的链孢霉中的删除导致CAT-3的高表达水平和抗H2 O2诱导的ROS胁迫。CTK-1的催化活性是这种反应所必需的。另一方面，CTK-1过表达导致CAT-3表达降低。ChIP分析显示，CTK-1在转录延伸期间磷酸化cat-3 ORF区域中Ser 2残基处的RNAPII CTD，并且CTK-1的缺失导致SET-2募集和H3 K36 me 3修饰的显著减少。因此，cat-3位点的组蛋白变得高度乙酰化以促进其转录。总之，这些结果表明，CTK复合物是通过影响其染色质结构的cat-3表达的负调节剂。
Clearance and adaptation to reactive oxygen species (ROS) are crucial for cell survival. As in other eukaryotes, the Neurospora catalases are the main enzymes responsible for ROS clearance and their expression are tightly regulated by the growth and environmental conditions. The RNA polymerase II carboxyl terminal domain (RNAPII CTD) kinase complex (CTK complex) is known as a positive elongation factor for many inducible genes by releasing paused RNAPII near the transcription start site and promoting transcription elongation. However, here we show that deletion of CTK complex components in Neurospora led to high CAT-3 expression level and resistance to H2O2-induced ROS stress. The catalytic activity of CTK-1 is required for such a response. On the other hand, CTK-1 overexpression led to decreased expression of CAT-3. ChIP assays shows that CTK-1 phosphorylates the RNAPII CTD at Ser2 residues in the cat-3 ORF region during transcription elongation and deletion of CTK-1 led to dramatic decreases of SET-2 recruitment and H3K36me3 modification. As a result, histones at the cat-3 locus become hyperacetylated to promote its transcription. Together, these results demonstrate that the CTK complex is negative regulator of cat-3 expression by affecting its chromatin structure.