CCAAT/enhancer-binding protein delta gene expression is mediated by autoregulation through downstream binding sites.

CCAAT/enhancer-binding protein delta (C/EBP delta) transcription factor is sharply induced at the early stage of the acute phase response. We previously reported that the C/EBP delta gene expression is induced by the acute-phase response factor/signal transducers and activators of transcription 3 (APRF/STAT3). However, the expression level of the C/EBP delta gene is relatively high up to several hours after the stimulation, whereas APRF/STAT3 is inactivated within one hour. In this report, we identified the two C/EBP delta binding sites at the downstream region of this gene. The binding analysis revealed that both of these sites bound recombinant C/EBP delta protein. A cotransfection analysis identified these sites as the cis-elements for the autoregulation. We conclude that the C/EBP delta gene is activated by APRF/STAT3, and the expression level is then maintained by an autoregulation mechanism.