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

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.
Authors	Eun Jin Lim, Thomas X Lu, Carine Blanchard, Marc E Rothenberg
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 286 Issue 15 Pg. 13193-204 (Apr 15 2011) ISSN: 1083-351X [Electronic] United States
PMID	21325281 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	CCL26 protein, human Chemokine CCL26 Chemokines, CC Histones Interleukin-13 STAT6 Transcription Factor STAT6 protein, human CREB-Binding Protein CREBBP protein, human
Topics	Acetylation CREB-Binding Protein (genetics, metabolism) Cell Line Chemokine CCL26 Chemokines, CC (biosynthesis) Epigenesis, Genetic (physiology) Histones (genetics, metabolism) Humans Interleukin-13 (genetics, metabolism) Response Elements (physiology) STAT6 Transcription Factor (genetics, metabolism) Transcription, Genetic (physiology)

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