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GATA-4 modulates C/EBP-dependent transcriptional activation of acute phase protein genes
Naomie Turgeon1, Dominic Rousseau, Evelyne Roy
1Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3001 12eme avenue nord, Sherbrooke, Que., Canada.
Abstract:
C/EBP transcription factors are involved in the regulation of the intestinal epithelial cell response to inflammatory stimuli. GATA transcription factors modulate C/EBP-dependent transcriptional activation in various cell types. We thus determined whether GATA-4 whose expression is restricted to epithelial cells, modulate C/EBP transcriptional activity and C/EBP-dependent acute phase protein expression in intestinal epithelial cells. Interaction between C/EBPdelta and GATA-4 required both C/EBPdelta leucine zipper and basic DNA-binding domains, and the GATA-4 C-terminal region. C/EBP isoforms and GATA-4 synergistically activated the alpha-acid glycoprotein gene while GATA-4 repressed thiostatin and haptoglobin C/EBP-dependent transactivation. In GATA-4 expressing intestinal epithelial cells, GATA-4 led to decreased C/EBPbeta and C/EBPdelta protein levels, and decreased thiostatin expression in response to IL-1beta and dexamethasone. This correlated with decreased C/EBPdelta recruitment to the thiostatin promoter, as assessed by chromatin immunoprecipitation assays. In contrast, increased AGP expression in response to dexamethasone correlated with increased basal histone H4 acetylation. Thus, GATA-4 may be involved in the establishment of specific intestinal epithelial cell C/EBP-dependent and C/EBP-independent transcriptional responses.
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