Autoregulated Induction of the Acute-Phase Response Transcription Factor Gene,agp/ebp

Abstract

AGP/EBP (C/EBPβ) is a key transcription factor responsible for transcriptional induction of many acute-phase protein genes. To characterize the regulation of this gene, we have isolated the mouse genomic DNA and sequenced the 5′-regulatory region. Using nuclear extracts from lipopolysaccharide (LPS)-stimulated or unstimulated mouse liver, three protein factor-binding motifs, UF1(−376 to −352), UF2(−254 to −223), and UF3(−220 to −190), as well as two Sp1 motifs (−309 to −277, and −264 to −241) were identified by DNase I footprinting assays. Biochemical analysis has shown that the AGP/EBP protein can bind to UF1 and UF2 sites, whereas an ubiquitous factor of unknown identity can bind to the UF3 site. Functional characterizations indicate that all of these factors play a major role in AGP/EBP induction. Thus, the agp/ebp gene is autoregulated during the acute-phase response.