MeCP2/H3meK9 are involved in IL-6 gene silencing in pancreatic adenocarcinoma cell lines.
The aim of the present study was to analyse the molecular mechanisms involved in the Interleukin-6 (IL-6) silencing in pancreatic adenocarcinoma cell lines. Our results demonstrate that TNF-alpha, a major IL-6 inducer, is able to induce IL-6 only in three out of six cell lines examined. 5-aza-2'-deoxycytidine (DAC), but not trichostatin A (TSA), activates the expression of IL-6 in all cell lines, indicating that DNA methylation, but not histone deacetylation, plays an essential role in IL-6 silencing. Indeed, the IL-6 upstream region shows a methylation status that correlates with IL-6 expression and binds MeCP2 and H3meK9 only in the non-expressing cell lines. Our results suggest that critical methylations located from positions -666 to -426 relative to the transcription start site of IL-6 may act as binding sites for MeCP2.
Dandrea
Mario
M
Department of Morphological and Biomedical Sciences, Section of Biochemistry, University of Verona, Verona, Italy.
Donadelli
Massimo
M
Costanzo
Chiara
C
Scarpa
Aldo
A
Palmieri
Marta
M
D000230:Adenocarcinoma / Q000235:genetics*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000378:metabolism; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D000077209:Decitabine; D020868:Gene Silencing; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics*; D000093242:Interleukin-6 Inhibitors
D001374:Azacitidine; D022763:CCAAT-Enhancer-Binding Protein-alpha; D004247:DNA; D000077209:Decitabine; D006877:Hydroxamic Acids; D015850:Interleukin-6; D051783:Methyl-CpG-Binding Protein 2; D016328:NF-kappa B; D000093242:Interleukin-6 Inhibitors; C497392:MECP2 protein, human; C012589:trichostatin A