The methylation status of the chemerin promoter region located from - 252 to + 258 bp regulates constitutive but not acute-phase cytokine-inducible chemerin expression levels

Sci Rep. 2020 Aug 13;10(1):13702. doi: 10.1038/s41598-020-70625-7.


Chemerin is a chemoattractant protein with adipokine properties encoded by the retinoic acid receptor responder 2 (RARRES2) gene. It has gained more attention in the past few years due to its multilevel impact on metabolism and immune responses. However, mechanisms controlling the constitutive and regulated expression of RARRES2 in a variety of cell types remain obscure. To our knowledge, this report is the first to show that DNA methylation plays an important role in the cell-specific expression of RARRES2 in adipocytes, hepatocytes, and B lymphocytes. Using luciferase reporter assays, we determined the proximal fragment of the RARRES2 gene promoter, located from - 252 to + 258 bp, to be a key regulator of transcription. Moreover, we showed that chemerin expression is regulated in murine adipocytes by acute-phase cytokines, interleukin 1β and oncostatin M. In contrast with adipocytes, these cytokines exerted a weak, if any, response in mouse hepatocytes, suggesting that the effects of IL-1β and OSM on chemerin expression is specific to fat tissue. Together, our findings highlight previously uncharacterized mediators and mechanisms that control chemerin expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Animals
  • Chemokines / genetics
  • Chemokines / metabolism*
  • DNA Methylation*
  • Gene Expression Regulation / drug effects*
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Interleukin-1beta / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oncostatin M / pharmacology*
  • Promoter Regions, Genetic*


  • Chemokines
  • IL1B protein, human
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-1beta
  • RARRES2 protein, human
  • chemerin protein, mouse
  • Oncostatin M