Identification of ribavirin-responsive cis-elements for GPAM suppression in the GPAM genome

Daichi Onomura, Shinya Satoh, Youki Ueda, Hiromichi Dansako, Nobuyuki Kato

Research output: Contribution to journalArticlepeer-review

Abstract

Glycerol-3-phosphate acyltransferase, mitochondrial (GPAM) is a rate-limiting enzyme catalyzing triglyceride synthesis. Recently, we demonstrated that the anti-viral drug ribavirin (RBV) reduces GPAM expression by downregulating CCAAT/enhancer-binding protein α (C/EBPα). However, the precise mechanisms of GPAM suppression have remained unclear. Here, we found that RBV suppressed GPAM expression by downregulating not only C/EBPα, but also sterol regulatory element-binding protein-1c (SREBP-1c). We also found that cis-elements regulated by C/EBPα and SREBP-1c functioned as distal and proximal enhancers, respectively, to express hepatocyte- and adipocytes-specific GPAM variants. These results imply that RBV disrupts formation of the enhancer machineries on the GPAM genome by downregulating both transcription factors. Our findings may contribute to the development of treatments for fatty liver diseases caused by aberrant triglyceride synthesis.

Original languageEnglish
Pages (from-to)148-154
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume533
Issue number1
DOIs
Publication statusPublished - Nov 26 2020
Externally publishedYes

Keywords

  • C/EBPα
  • GPAM
  • Ribavirin
  • SREBP-1c
  • cis-element

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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