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Regulation of C/EBPδ-dependent transactivation by histone deacetylases in intestinal epithelial cells

✍ Scribed by Naomie Turgeon; Caroline Valiquette; Mylène Blais; Sophie Routhier; Ernest G. Seidman; Claude Asselin


Publisher
John Wiley and Sons
Year
2008
Tongue
English
Weight
288 KB
Volume
103
Category
Article
ISSN
0730-2312

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✦ Synopsis


Abstract

The C/EBPδ transcription factor is involved in the positive regulation of the intestinal epithelial cell acute phase response. C/EBPδ regulation by histone deacetylases (HDACs) during the course of inflammation remains to be determined. Our aim was to examine the effect of HDACs on C/EBPδ‐dependent regulation of haptoglobin, an acute phase protein induced in intestinal epithelial cells in response to pro‐inflammatory cytokines. HDAC1, HDAC3, and HDAC4 were expressed in intestinal epithelial cells, as determined by Western blot. GST pull‐down assays showed specific HDAC1 interactions with the transcriptional activation and the b‐ZIP C/EBPδ domains, while the co‐repressor mSin3A interacts with the C‐terminal domain. Immunoprecipitation assays confirmed the interaction between HDAC1 and the N‐terminal C/EBPδ amino acid 36–164 domain. HDAC1 overexpression decreased C/EBPδ transcriptional activity of the haptoglobin promoter, as assessed by transient transfection and luciferase assays. Chromatin immunoprecipitation analysis showed a displacement of HDAC1 from the haptoglobin promoter in response to inflammatory stimuli and an increased acetylation of histone H3 and H4. HDAC1 silencing by shRNA expression increased both basal and IL‐1β‐induced haptoglobin mRNA levels in epithelial intestinal cells. Our results suggest that interactions between C/EBPs and HDAC1 negatively regulate C/EBPδ‐dependent haptoglobin expression in intestinal epithelial cells. J. Cell. Biochem. 103: 1573–1583, 2008. © 2007 Wiley‐Liss, Inc.


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