Abstract
Bacterial lipopolysaccharide (LPS) induces release of inflammatory mediators both in immune and epithelial cells. We investigated whether changes of epigenetic marks, including selected histone modification and DNA methylation, may drive or accompany the activation of COX-2 gene in HT-29 human intestinal epithelial cells upon exposure to LPS. Here we describe cyclical histone acetylation (H3), methylation (H3K4, H3K9, H3K27) and DNA methylation changes occurring at COX-2 gene promoter overtime after LPS stimulation. Histone K27 methylation changes are carried out by the H3 demethylase JMJD3 and are essential for COX-2 induction by LPS. The changes of the histone code are associated with cyclical methylation signatures at the promoter and gene body of COX-2 gene.
MeSH terms
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CpG Islands / genetics
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Cyclooxygenase 2 / genetics*
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Cyclooxygenase 2 / metabolism
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DNA Methylation / genetics*
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Enzyme Activation / drug effects
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Epigenesis, Genetic / drug effects
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Epithelial Cells / drug effects
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Epithelial Cells / enzymology*
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Gene Silencing / drug effects
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HT29 Cells
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Histones / metabolism*
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Humans
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Intestines / cytology*
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Jumonji Domain-Containing Histone Demethylases / metabolism
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Lipopolysaccharides / pharmacology*
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Lysine / metabolism
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Promoter Regions, Genetic
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RNA, Small Interfering / metabolism
Substances
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Histones
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Lipopolysaccharides
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RNA, Small Interfering
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Jumonji Domain-Containing Histone Demethylases
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KDM6B protein, human
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Cyclooxygenase 2
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PTGS2 protein, human
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Lysine
Grants and funding
This work was supported by grant from Epigenomics Flagship Project – EPIGEN, C.N.R. to LCh, by POR Campania FSE 2007-2013, Project CRÈME, to TA, by Regione Campania, l.5, to LCh, and by Associazione Italiana per la Ricerca sul Cancro – AIRC (IG 16983) to VEA. LCo, fellowship by EPIGEN Flagship Project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.