Elongin functions as a loading factor for Mediator at ATF6α-regulated ER stress response genes

• Published in: Proceedings of the National Academy of Sciences - PNAS 2021-09, Vol.118 (39), p.1-10
• Main Authors: He, Yanfeng, Sato, Shigeo, Tomomori-Sato, Chieri, Chen, Shiyuan, Goode, Zach H., Conaway, Joan W., Conaway, Ronald C.
• Format: Article
• Language: English
• Subjects: Activating Transcription Factor 6 - genetics; Activating Transcription Factor 6 - metabolism; Animals; Biological Sciences; Cyclin-dependent kinase 8; Depletion; DNA-directed RNA polymerase; Elongin - genetics; Elongin - metabolism; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - pathology; Endoplasmic Reticulum Stress; Enhancers; Gene Expression Regulation; Genes; HeLa Cells; Humans; Kinases; Mediator Complex - genetics; Mediator Complex - metabolism; Promoter Regions, Genetic; Rats; RNA polymerase; RNA polymerase II; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; Signal Transduction; Stress response; Transcription activation; Transcription factors; Transcriptional Activation
• ISSN: 0027-8424; 1091-6490
• 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.