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CCAAT/enhancer-binding protein delta gene expression is mediated by autoregulation through downstream binding sites
T Yamada1, T Tsuchiya, S Osada
1Laboratory of Environmental Biochemistry, School of Pharmaceutical Sciences, Osaka University, Japan.
Biochemical and Biophysical Research Communications
|January 24, 1998
Summary
CCAAT/enhancer-binding protein delta (C/EBP delta) is induced during the acute phase response. This study reveals C/EBP delta autoregulation maintains its gene expression after initial APRF/STAT3 activation.
Area of Science:
- Molecular biology
- Gene regulation
- Transcription factors
Background:
- CCAAT/enhancer-binding protein delta (C/EBP delta) is a key transcription factor in the acute phase response.
- Previous work showed APRF/STAT3 induces C/EBP delta gene expression.
- A discrepancy exists between the prolonged C/EBP delta expression and the transient APRF/STAT3 activity.
Purpose of the Study:
- To investigate the mechanism maintaining C/EBP delta gene expression.
- To identify cis-regulatory elements involved in C/EBP delta gene expression.
- To elucidate the role of autoregulation in C/EBP delta expression.
Main Methods:
- Identification of C/EBP delta binding sites downstream of the C/EBP delta gene.
- In vitro binding analysis using recombinant C/EBP delta protein.
- Cotransfection assays to assess cis-element function.
Main Results:
- Two C/EBP delta binding sites were identified in the downstream region of the C/EBP delta gene.
- Both identified sites demonstrated binding with recombinant C/EBP delta protein.
- Cotransfection analysis confirmed these sites function as cis-elements for autoregulation.
Conclusions:
- The C/EBP delta gene is initially activated by APRF/STAT3.
- A C/EBP delta autoregulation mechanism maintains sustained gene expression.
- This autoregulation ensures prolonged C/EBP delta levels during the acute phase response.