Cyclical DNA Methylation and Histone Changes Are Induced by LPS to Activate COX-2 in Human Intestinal Epithelial Cells

Tiziana Angrisano; Raffaela Pero; Mariarita Brancaccio; Lorena Coretti; Ermanno Florio; Antonio Pezone; Viola Calabrò; Geppino Falco; Simona Keller; Francesca Lembo; Vittorio Enrico Avvedimento; Lorenzo Chiariotti

doi:10.1371/journal.pone.0156671

Cyclical DNA Methylation and Histone Changes Are Induced by LPS to Activate COX-2 in Human Intestinal Epithelial Cells

PLoS One. 2016 Jun 2;11(6):e0156671. doi: 10.1371/journal.pone.0156671. eCollection 2016.

Authors

Tiziana Angrisano¹, Raffaela Pero^{2

3}, Mariarita Brancaccio², Lorena Coretti^{2

3}, Ermanno Florio^{2

3}, Antonio Pezone^{2

3}, Viola Calabrò¹, Geppino Falco¹, Simona Keller^{2

3}, Francesca Lembo⁴, Vittorio Enrico Avvedimento², Lorenzo Chiariotti^{2

3}

Affiliations

¹ Dipartimento di Biologia, Università degli Studi di Napoli "Federico II", Monte Sant'Angelo via Cintia 21, 80126 Naples, Italy.
² Dipartimento di Medicina Molecolare e Biotecnologie Mediche, via S. Pansini, 5, 80131 Naples, Italy.
³ Istituto di Endocrinologia ed Oncologia Sperimentale C.N.R., via S. Pansini, 5, 80131 Naples, Italy.
⁴ Dipartimento di Farmacia, Università degli Studi di Napoli "Federico II", via D. Montesano 47, 80131 Naples, Italy.

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

CpG Islands / genetics
Cyclooxygenase 2 / genetics*
Cyclooxygenase 2 / metabolism
DNA Methylation / genetics*
Enzyme Activation / drug effects
Epigenesis, Genetic / drug effects
Epithelial Cells / drug effects
Epithelial Cells / enzymology*
Gene Silencing / drug effects
HT29 Cells
Histones / metabolism*
Humans
Intestines / cytology*
Jumonji Domain-Containing Histone Demethylases / metabolism
Lipopolysaccharides / pharmacology*
Lysine / metabolism
Promoter Regions, Genetic
RNA, Small Interfering / metabolism

Substances

Histones
Lipopolysaccharides
RNA, Small Interfering
Jumonji Domain-Containing Histone Demethylases
KDM6B protein, human
Cyclooxygenase 2
PTGS2 protein, human
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.