Epigenetic regulation of the IL-13-induced human eotaxin-3 gene by CREB-binding protein-mediated histone 3 acetylation

J Biol Chem. 2011 Apr 15;286(15):13193-204. doi: 10.1074/jbc.M110.210724. Epub 2011 Feb 16.

Abstract

The etiology of a variety of chronic inflammatory disorders has been attributed to the interaction of genetic and environmental factors. Herein, we identified a link between epigenetic regulation and IL-13-driven eotaxin-3 in the pathogenesis of chronic allergic inflammation. We first demonstrated that the cAMP-responsive element (CRE) site in the eotaxin-3 promoter affects IL-13-induced eotaxin-3 promoter activity. Furthermore, the CRE-binding protein-binding protein (CBP), a histone acetyltransferase, induced base-line and IL-13-induced eotaxin-3 promoter activity. Additionally, IL-13 treatment promoted global histone 3 acetylation as well as the formation of a complex containing CBP and STAT6 and the subsequent acetylation of histone 3 at the eotaxin-3 promoter. CBP gene silencing decreased IL-13-induced transcription of eotaxin-3. Conversely, inhibition of histone deacetylation increased IL-13-induced eotaxin-3 production. Clinical studies demonstrated markedly increased global acetylation of histone 3 in the inflamed tissue of patients with allergic inflammation. Collectively, these results identify an epigenetic mechanism involving CBP and chromatin remodeling in regulating IL-13-induced chemokine transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • CREB-Binding Protein / genetics
  • CREB-Binding Protein / metabolism*
  • Cell Line
  • Chemokine CCL26
  • Chemokines, CC / biosynthesis*
  • Epigenesis, Genetic / physiology*
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Interleukin-13 / genetics
  • Interleukin-13 / metabolism*
  • Response Elements / physiology*
  • STAT6 Transcription Factor / genetics
  • STAT6 Transcription Factor / metabolism
  • Transcription, Genetic / physiology

Substances

  • CCL26 protein, human
  • Chemokine CCL26
  • Chemokines, CC
  • Histones
  • Interleukin-13
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • CREB-Binding Protein
  • CREBBP protein, human