Gene expression of CCAAT/enhancer-binding protein delta mediated by autoregulation is repressed by related gene family proteins.

CCAAT/enhancer-binding protein delta (C/EBPdelta) transcription factor is rapidly induced at an early stage of acute phase response. We previously reported that this induction was mainly mediated by acute phase response factor/signal transducers and activators of transcription 3 (APRF/STAT3). Furthermore, the high expression level of C/EBPdelta is maintained by autoregulation mechanisms through the C/EBPdelta binding sites located downstream of C/EBPdelta gene. Thereafter, the expression of C/EBPdelta gene decreases rapidly to the basal level. However, these mechanisms are still unknown. According to both transfection and DNA binding analyses, liver-enriched inhibitory protein (LIP), the shorter form of C/EBPbeta and C/EBP-homologous protein 10 (CHOP10), were found to inhibit C/EBPdelta gene expression. DNA binding analysis has further indicated that both LIP and CHOP10 form heterodimers with C/EBPdelta, and inhibit the binding of C/EBPdelta homodimer to the C/EBPdelta binding sites located downstream of C/EBPdelta gene. Taken together, these findings indicated that the maintained expression of C/EBPdelta gene by autoregulation was inhibited and decreased to the basal level as a result of the competition of other C/EBP family proteins. Thus, C/EBPdelta gene expression is mediated by the gene regulation circuit through the downstream C/EBPdelta binding sites.