Yin and yang regulation of liver x receptor α signaling control of cholesterol metabolism by poly(Adp-ribose) polymerase 1

Fengxiao Zhang, Cheng Wang, Yuhan Jiang, Kun Huang, Fangmei Liu, Meng Du, Xi Luo, Dan Huang, Kai Huang

Research output: Contribution to journalArticlepeer-review

Abstract

Liver X receptor α (LXRα) controls a set of key genes involved in cholesterol metabolism. However, the molecular mechanism of this regulation remains unknown. The regulatory role of poly(ADP-ribose) polymerase 1 (PARP1) in cholesterol metabolism in the liver was examined. Activation of PARP1 in the liver suppressed LXRα sensing and prevented upregulation of genes involved in HCD-induced cholesterol disposal. Mechanistically, LXRα was poly(ADP-ribosyl)ated by activated PARP1, which decreased DNA binding capacity of LXRα, thus preventing its recruitment to the target promoter. Intriguingly, we found that unactivated PARP1 was indispensable for LXRα transactivation and target expression. Further exploration identified unactivated PARP1 as an essential component of the LXRα-promoter complex. Taken together, the results indicate that activated PARP1 suppresses LXRα activation through poly(ADP-ribosyl)ation, while unactivated PARP1 promotes LXRα activation through physical interaction. PARP1 is a pivotal regulator of LXRα signaling and cholesterol metabolism in the liver.

Original languageEnglish (US)
Pages (from-to)2868-2882
Number of pages15
JournalInternational Journal of Biological Sciences
Volume16
Issue number15
DOIs
StatePublished - 2020
Externally publishedYes

Keywords

  • Cholesterol metabolism
  • LXRα
  • PARP1

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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