Changes in chromatin structure and methylation of the human interleukin-1beta gene during monopoiesis.
Interleukin-1beta (IL-1beta) induces the expression of a variety of proteins responsible for acute inflammation and chronic inflammatory diseases. However, the molecular regulation of IL-1beta expression in myeloid differentiation has not been elucidated. In this study the chromatin structure of the IL-1beta promoter and the impact of methylation on IL-1beta expression in monocytic development were examined. The results revealed that the IL-1beta promoter was inaccessible in undifferentiated promyeloid HL-60 cells but highly accessible in differentiated monocytic cells which additionally acquired the ability to produce IL-1beta. Accessibilities of differentiated cells were comparable to those of primary monocytes. Lipopolysaccharide (LPS) stimulation did not affect promoter accessibility in promyeloid and monocytic HL-60 cells, demonstrating that the chromatin remodelling of the IL-1beta promoter depends on differentiation and not on the transcriptional status of the cell. Demethylation via 5-aza-2'-deoxycytodine led to the induction of IL-1beta expression in undifferentiated and differentiated cells, which could be increased after LPS stimulation. Our data indicate that the IL-1beta promoter is reorganized into an open poised conformation during monopoiesis being a privilege of mature monocytes but not of the entire myeloid lineage. As a second mechanism, IL-1beta expression is regulated by methylation acting independently of the developmental stage of myeloid cells.
Institute of Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
Inga
I
Wessels
Daniela
D
Fleischer
Lothar
L
Rink
Peter
P
Uciechowski
D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology*; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008836:Micrococcal Nuclease / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D038042:Myelopoiesis / Q000187:drug effects / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics
D016207:Cytokines; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C012589:trichostatin A; D000077209:Decitabine; D004247:DNA; D015254:DNA Modification Methylases; D008836:Micrococcal Nuclease; D002117:Calcitriol; D001374:Azacitidine