title: Dynamic CpG-DNA methylation of Il10 and Il19 in CD4+ T lymphocytes and macrophages: effects on tissue-specific gene expression.
abstract: The IL-10 family of cytokines consists of 9 members, including the immune-regulatory IL-10;  Il19 is in close physical relationship with Il10 in the so-called IL-10 cytokine cluster on chromosome 1q32. While IL-10 is ubiquitously expressed, IL-19 expression is restricted to myeloid and epithelial cells. Little is known about molecular mechanisms that control tissue-specific expression of IL-10, and IL-19. Modifications in CpG-DNA methylation are a key mechanism in controlling transcription. Using bisulfite sequencing, we demonstrate that murine Il19 is methylated in CD4+ T lymphocytes. Macrophages display site-specific demethylation of Il19. The ubiquitously expressed Il10 gene is methylated to a lower degree and exhibits tissue-specific methylation patterns. DNA demethylation with 5-azacytidine resulted in an induction of IL-10, and IL-19 expression in CD4+ T cells, and CpG-DNA methylation through DNMT3a resulted in transcriptional silencing in macrophages. Thus, our findings suggest a role of CpG-DNA methylation in the regulation of Il10 and Il19.
authors.affiliation: Klinik und Poliklinik für Kinder- und Jugendmedizin, Neonatologie und Intensivmedizin, Dresden, Germany.
authors.forename: S R
authors.initials: SR
authors.lastname: Hofmann
authors.forename: J
authors.initials: J
authors.lastname: Möller
authors.forename: T
authors.initials: T
authors.lastname: Rauen
authors.forename: D
authors.initials: D
authors.lastname: Paul
authors.forename: M
authors.initials: M
authors.lastname: Gahr
authors.forename: Z
authors.initials: Z
authors.lastname: Rösen-Wolff
authors.forename: S
authors.initials: S
authors.lastname: Brenner
authors.forename: C M
authors.initials: CM
authors.lastname: Hedrich
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000235:genetics; D001374:Azacitidine / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D018899:CpG Islands / Q000235:genetics*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007125:Immunogenetics; D016753:Interleukin-10 / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D008213:Lymphocyte Activation / Q000235:genetics; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism; D009928:Organ Specificity; D012097:Repressor Proteins / Q000235:genetics
chemical_list: C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse; D004791:Enzyme Inhibitors; C421250:IL19 protein, human; D007378:Interleukins; D012097:Repressor Proteins; D016753:Interleukin-10; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D001374:Azacitidine