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J Lipid Res. 2021;62:100063. doi: 10.1016/j.jlr.2021.100063. Epub 2021 Mar 08.

25-Hydroxycholesterol 3-sulfate is an endogenous ligand of DNA methyltransferases in hepatocytes.

Journal of lipid research

Yaping Wang, Weiqi Lin, James E Brown, Lanming Chen, Williams M Pandak, Phillip B Hylemon, Shunlin Ren

Affiliations

  1. Department of Internal Medicine, Virginia Commonwealth University/McGuire VA Medical Centre, Richmond, VA, USA; College of Food Science and Technology, Shanghai Ocean University, Shanghai, China.
  2. DURECT Corporation, Cupertino, CA, USA.
  3. College of Food Science and Technology, Shanghai Ocean University, Shanghai, China.
  4. Department of Internal Medicine, Virginia Commonwealth University/McGuire VA Medical Centre, Richmond, VA, USA.
  5. Department of Internal Medicine, Virginia Commonwealth University/McGuire VA Medical Centre, Richmond, VA, USA. Electronic address: [email protected].

PMID: 33705741 PMCID: PMC8058565 DOI: 10.1016/j.jlr.2021.100063

Abstract

The oxysterol sulfate, 25-hydroxycholesterol 3-sulfate (25HC3S), has been shown to play an important role in lipid metabolism, inflammatory response, and cell survival. However, the mechanism(s) of its function in global regulation is unknown. The current study investigates the molecular mechanism by which 25HC3S functions as an endogenous epigenetic regulator. To study the effects of oxysterols/sterol sulfates on epigenetic modulators, 12 recombinant epigenetic enzymes were used to determine whether 25HC3S acts as their endogenous ligand. The enzyme kinetic study demonstrated that 25HC3S specifically inhibited DNA methyltransferases (DNMTs), DNMT1, DNMT3a, and DNMT3b with IC

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords: CpG methylation; DNMT; MAPK-ERK signaling; calcium-AMPK signaling; cholesterol metabolites; high glucose; metabolic regulation; oxysterol; oxysterol sulfate; oxysterol sulfation

Conflict of interest statement

Conflict of interest S. R. and Virginia Commonwealth University obtained license-related payments from DURECT Corporation, Cupertino, CA. All other authors declare that they have no conflicts of inter

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