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

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 1 beta and oncostatin M. In contrast with adipocytes, these cytokines exerted a weak, if any, response in mouse hepatocytes, suggesting that the effects of IL-1 beta and OSM on chemerin expression is specific to fat tissue. Together, our findings highlight previously uncharacterized mediators and mechanisms that control chemerin expression.