論文

国際誌
2020年11月26日

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

Biochemical and biophysical research communications
  • Daichi Onomura
  • ,
  • Shinya Satoh
  • ,
  • Youki Ueda
  • ,
  • Hiromichi Dansako
  • ,
  • Nobuyuki Kato

533
1
開始ページ
148
終了ページ
154
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2020.08.112

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.

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2020.08.112
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32933750
ID情報
  • DOI : 10.1016/j.bbrc.2020.08.112
  • PubMed ID : 32933750

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