Stowers Institute for Medical Research, Kansas City, MO 64110.
Stowers Institute for Medical Research, Kansas City, MO 64110;
Proc Natl Acad Sci U S A. 2021 Sep 28;118(39). doi: 10.1073/pnas.2108751118.
The bZIP transcription factor ATF6α is a master regulator of endoplasmic reticulum (ER) stress response genes. In this report, we identify the multifunctional RNA polymerase II transcription factor Elongin as a cofactor for ATF6α-dependent transcription activation. Biochemical studies reveal that Elongin functions at least in part by facilitating ATF6α-dependent loading of Mediator at the promoters and enhancers of ER stress response genes. Depletion of Elongin from cells leads to impaired transcription of ER stress response genes and to defects in the recruitment of Mediator and its CDK8 kinase subunit. Taken together, these findings bring to light a role for Elongin as a loading factor for Mediator during the ER stress response.
bZIP 转录因子 ATF6α 是内质网（ER）应激反应基因的主要调节因子。在本报告中，我们确定多功能 RNA 聚合酶 II 转录因子 Elongin 是 ATF6α 依赖性转录激活的辅助因子。生化研究表明，Elongin 的功能至少部分是通过促进 ATF6α 依赖性将 Mediator 加载到 ER 应激反应基因的启动子和增强子上。从细胞中耗尽 Elongin 会导致 ER 应激反应基因的转录受损，并导致 Mediator 及其 CDK8 激酶亚基的募集缺陷。总之，这些发现揭示了 Elongin 在 ER 应激反应中作为 Mediator 加载因子的作用。
