Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites
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Binding, Competitive
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CCAAT-Enhancer-Binding Protein-beta / genetics
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CCAAT-Enhancer-Binding Protein-beta / metabolism
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CCAAT-Enhancer-Binding Protein-beta / pharmacology
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CCAAT-Enhancer-Binding Protein-beta / physiology*
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CCAAT-Enhancer-Binding Protein-delta
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CCAAT-Enhancer-Binding Proteins / antagonists & inhibitors
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CCAAT-Enhancer-Binding Proteins / genetics*
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CCAAT-Enhancer-Binding Proteins / metabolism
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CCAAT-Enhancer-Binding Proteins / pharmacology
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CCAAT-Enhancer-Binding Proteins / physiology*
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology
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Dimerization
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Humans
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Rats
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STAT3 Transcription Factor
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Trans-Activators / metabolism
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Trans-Activators / physiology
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Transcription Factor CHOP
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / pharmacology
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Transcription Factors / physiology*
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Transcriptional Activation / drug effects
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Transcriptional Activation / physiology
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Transfection
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Tumor Cells, Cultured
Substances
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CCAAT-Enhancer-Binding Protein-beta
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CCAAT-Enhancer-Binding Proteins
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CEBPD protein, human
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Cebpd protein, rat
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DDIT3 protein, human
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DNA-Binding Proteins
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Ddit3 protein, rat
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STAT3 Transcription Factor
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STAT3 protein, human
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Stat3 protein, rat
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Trans-Activators
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Transcription Factors
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CCAAT-Enhancer-Binding Protein-delta
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Transcription Factor CHOP