CCAAT/enhancer-binding protein-beta regulates interferon-induced transcription through a novel element.
We have described previously a novel interferon (IFN)-responsive cis-acting enhancer element called gamma-IFN-activated transcriptional element (GATE). GATE is distinct from the known IFN-stimulated elements and binds to novel transacting factors. To identify the gamma-IFN-responsive transacting factors that interact with GATE, we have screened a cDNA expression library derived from IFN-gamma-stimulated murine macrophage cell line and isolated three different cDNAs. Among these is a gene coding for the pleiotropic transcription factor, CCAAT/enhancer-binding protein-beta (C/EBP-beta). We report here that the gene for C/EBP-beta binds to GATE and induces gene expression. A mutant C/EBP-beta interferes with the IFN-gamma-stimulated transcription of the ISGF3gamma (p48) promoter. Other members of the C/EBP family do not cause these effects. Interestingly, the expression of C/EBP-beta, not the other members of its family, is induced by IFN-gamma. These studies thus identify a novel role for C/EBP-beta in the IFN-signaling pathways.
Roy
S K
SK
Marlene and Stewart Greenebaum Cancer Center, Department of Microbiology and Immunology, Molecular and Cellular Biology Program, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Wachira
S J
SJ
Weihua
X
X
Hu
J
J
Kalvakolanu
D V
DV
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051790:G-Box Binding Factors; D005786:Gene Expression Regulation; D015723:Gene Library; D007371:Interferon-gamma / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D014176:Protein Biosynthesis; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D022762:CCAAT-Enhancer-Binding Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D051790:G-Box Binding Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D007371:Interferon-gamma