ATF6α stimulates cholesterogenic gene expression and de novo cholesterol synthesis

Biosci Biotechnol Biochem. 2013;77(8):1734-8. doi: 10.1271/bbb.130295. Epub 2013 Aug 7.


The activating transcription factor 6α (ATF6α) is a sensor of the endoplasmic reticulum stress response that regulates the expression of genes involved in the unfolded protein response. Here we found that forced expression of a constitutively active form of ATF6α, ATF6(N), stimulated the expression of cholesterogenic genes, including 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase, HMG-CoA synthase, and squalene synthase, and de novo cholesterol synthesis in hepatoma Huh-7 cells. An ATF6α mutant lacking the DNA-binding domain ATF6(N)ΔbZip failed to show these effects. Luciferase assays indicated that ATF6(N) overexpression stimulated the promoter activities of HMG-CoA reductase, HMG-CoA synthase, and squalene synthase. Chromatin immunoprecipitation assays revealed that ATF6(N) interacted with the promoter region of the HMG-CoA synthase gene. Collectively, these results indicate that ATF6α can regulate de novo cholesterol synthesis through stimulation of cholesterogenic gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 6 / genetics*
  • Activating Transcription Factor 6 / metabolism
  • Cholesterol / biosynthesis*
  • Cholesterol / chemistry
  • Endoplasmic Reticulum / enzymology*
  • Endoplasmic Reticulum Stress*
  • Farnesyl-Diphosphate Farnesyltransferase / genetics
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl-CoA Synthase / genetics
  • Promoter Regions, Genetic
  • RNA, Messenger


  • ATF6 protein, human
  • Activating Transcription Factor 6
  • RNA, Messenger
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases
  • Hydroxymethylglutaryl-CoA Synthase
  • Farnesyl-Diphosphate Farnesyltransferase