摘要：SummaryThe innate immune system is an immediate defense against infectious pathogens by the production of inflammatory cytokines and other mediators. Deficiencies of epigenetic regulatory enzymes, such asTet1andDnmt1, cause dysregulation of cytokine expression. However, it is unclear if DNA methylation at a single CpG dinucleotide in a specific gene locus can regulate gene expression. In this study, we demonstrated that CpG+286 and CpG+348 in exon 2 of theIl6gene are similar in various primary mouse cells. In lipopolysaccharide-stimulated condition, hypomethylated CpG+286 promotedIl6expression whereas deletion of CpG+348 led to a reduction inIl6expression associated with enhanced CTCF binding to theIl6locus. Moreover, hypomethylation at CpG+286 in alveolar macrophages from aged mice led to higherIl6expression in response to LPS compared with young mice. Thus, DNA methylation at specific CpG dinucleotides plays an important regulatory role inIl6expression.Graphical abstractDisplay OmittedHighlights•TET enzymes regulate DNA methylation atIl6TIS region and controlIl6expression•DNA methylation level at CpG+286 in theIl6locus directly controlsIl6expression•Methylated CpG+348 regulatesIl6expression and CTCF recruitment to theIl6locus•Methylation of CpG+286 in alveolar macrophages controls age-relatedIl6expressionImmunology; Molecular biology
