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.
Tanabe
A
A
Laboratory of Environmental Biochemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Kumahara
C
C
Osada
S
S
Nishihara
T
T
Imagawa
M
M
D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D019281:Dimerization; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D051381:Rats; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497252:CEBPD protein, human; C497254:Cebpd protein, rat; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; C497251:Ddit3 protein, rat; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494088:Stat3 protein, rat; D015534:Trans-Activators; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta; D051742:Transcription Factor CHOP