Promoter-specific relevance of histone modifications induced by dexamethasone during the regulation of pro-inflammatory mediators.
Glucocorticosteroids (GCs) are widely used to treat different kinds of chronic inflammatory and immune diseases through transcriptional regulation of inflammatory genes. Modulation of gene expression by GCs is known to occur through diverse mechanisms of varying relevance to specific classes of genes. Epigenetic modifications are indeed a pivotal regulatory feature of glucocorticoid receptor and other transcription factors. In this study, histone post-translational modifications were investigated for their involvement in the regulation of selected pro-inflammatory genes - expressed in human monocyte-derived macrophages - in response to treatment with synthetic GC dexamethasone (DEX). We show that histone tail acetylation status is modified following DEX administration, through distinct and alternative mechanisms at the promoters of interleukin-8 and interleukin-23. In addition to histone H3 acetylation, our results demonstrate that H3 lysine 4 trimethylation is affected following drug treatment.
Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Sezione di Biochimica e Biologia Molecolare "G. Fornaini", Via A. Saffi 2, 61029 Urbino, PU, Italy. Electronic address: linda.palma@uniurb.it.
Linda
L
Palma
Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Sezione di Biotecnologie, Laboratorio di Patologia Molecolare "M. PaoLa", Via Arco d'Augusto 2, 61032 Fano, PU, Italy.
Stefano
S
Amatori
Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Sezione di Biochimica e Biologia Molecolare "G. Fornaini", Via A. Saffi 2, 61029 Urbino, PU, Italy.
Ivan
I
Cruz Chamorro
Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Sezione di Biotecnologie, Laboratorio di Patologia Molecolare "M. PaoLa", Via Arco d'Augusto 2, 61032 Fano, PU, Italy.
Mirco
M
Fanelli
Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo", Sezione di Biochimica e Biologia Molecolare "G. Fornaini", Via A. Saffi 2, 61029 Urbino, PU, Italy.
Mauro
M
Magnani
D000107:Acetylation / Q000187:drug effects; D002843:Chromatin / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000235:genetics*; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D009000:Monocytes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational / Q000235:genetics*
D002843:Chromatin; D006657:Histones; D053759:Interleukin-23; D016209:Interleukin-8; D003907:Dexamethasone
Dexamethasone; Histone acetylation; Histone methylation; IL-23; IL-8; Macrophage