GATA-4 modulates C/EBP-dependent transcriptional activation of acute phase protein genes.
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.
Turgeon
Naomie
N
Département d'anatomie et biologie cellulaire, Faculté de médecine et des sciences de la santé, Université de Sherbrooke, 3001 12eme avenue nord, Sherbrooke, Que., Canada.
Rousseau
Dominic
D
Roy
Evelyne
E
Asselin
Claude
C
D000209:Acute-Phase Proteins / Q000235:genetics*; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D007704:Kininogens / Q000235:genetics; D051379:Mice; D051381:Rats; D015533:Transcriptional Activation
D000209:Acute-Phase Proteins; D022762:CCAAT-Enhancer-Binding Proteins; C405462:CCAAT-enhancer-binding protein-gamma; D002843:Chromatin; D050991:GATA4 Transcription Factor; D007704:Kininogens