## Abstract “Loss of function” alterations in growth inhibitory signal transduction pathways are common in cancer cells. In this study, we show that growth arrest (GA) treatments—serum and growth factor withdrawal and growth inhibitory IL‐6 family cytokines (Interleukin‐6 and Oncostatin M (OSM))—in
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
No coin nor oath required. For personal study only.
✦ 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.
📜 SIMILAR VOLUMES
In vitro experiments have shown that the establishment of cell-cell contacts in intestinal epithelial cell cultures is a critical step in initiating ERK inhibition, cell cycle arrest, and induction of the differentiation process. Herein, we determined the mechanisms through which E-cadherin-mediated
## Abstract CCAAT/enhancer binding protein δ (C/EBPδ) plays a key role in mammary epithelial cell G~0~ growth arrest. C/EBPδ gene expression is down‐regulated in rodent mammary tumorigenesis and in human breast cancer, suggesting that “loss of function” alterations in C/EBPδ gene expression are com