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Regulation of C/EBPδ‐dependent transcriptional activity by transcriptional repressors
Author(s) -
Asselin Claude,
Turgeon Naomie,
Blais Mylène
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1435-d
The C/EBPδ transcription factor is involved in the positive regulation of the intestinal epithelial cell acute phase response. However, C/EBPδ negative regulation by transcriptional repressors during inflammation remains to be determined. We verified the role of histone deacetylases (HDACs) and the mSin3A corepressor in C/EBPδ‐dependent regulation of haptoglobin, an acute phase protein induced in intestinal epithelial cells. METHODS We determined HDACs expression by immunofluorescence and Western Blot in intestinal epithelial cells. We analysed C/EBPδ interaction with HDACs and the mSin3A corepressor, by GST pull‐down assays and immunoprecipitation assays. Finally, by transient transfections and luciferase assays, we determined the consequence of HDACs overexpression on haptoglobin induction. RESULTS HDAC1 and HDAC3 were differentially expressed during intestinal epithelial cell differentiation. GST pull‐down assays showed specific HDAC1 and HDAC3 interactions with the transcriptional activation and the b‐ZIP C/EBPδ domains. Immunoprecipitation assays confirmed the interaction between HDAC1 and C/EBPδ. GST pull‐down assays showed a specific interaction between mSin3A and the C‐terminal C/EBPδ region. Overexpression of HDAC1 and HDAC3 decreased C/EBPδ transcriptional activity of the haptoglobin promoter.CONCLUSION Our results suggest that interactions between C/EBPδ, HDACs and mSin3A negatively regulate C/EBPδ‐dependent haptoglobin expression in intestinal epithelial cells.