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

Proc Natl Acad Sci U S A. 2021 Sep 28;118(39):e2108751118. doi: 10.1073/pnas.2108751118.

Abstract

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.

Keywords: Mediator; RNA polymerase II; enhancer; transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 6 / genetics
  • Activating Transcription Factor 6 / metabolism*
  • Animals
  • Elongin / genetics
  • Elongin / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / pathology
  • Endoplasmic Reticulum Stress*
  • Gene Expression Regulation*
  • HeLa Cells
  • Humans
  • Mediator Complex / genetics
  • Mediator Complex / metabolism*
  • Promoter Regions, Genetic
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism*
  • Rats
  • Signal Transduction
  • Transcriptional Activation

Substances

  • Activating Transcription Factor 6
  • Elongin
  • MED23 protein, human
  • MED26 protein, human
  • Mediator Complex
  • RNA Polymerase II