CCAAT-enhancer-binding proteins (C/EBP) regulate the tissue specific activity of the CD11c integrin gene promoter through functional interactions with Sp1 proteins.
The CD11c/CD18 integrin binds lipopolysaccharide, fibrinogen, and heparin, and mediates leukocyte adhesion, spreading, and migration. CD11c/CD18 is primarily found on myeloid cells and its expression is regulated during myeloid differentiation by transcriptional mechanisms acting on the CD11c gene promoter. We now describe that CCAAT/enhancer-binding proteins (C/EBP) contribute to the basal, tissue-specific and developmentally regulated activity of the CD11c promoter. A C/EBP-binding site within the CD11c promoter (CEBP-80) is bound by CEBPalpha in undifferentiated U937 cells and by C/EBPalpha- and C/EBPbeta-containing dimers in phorbol 12-myristate 13-acetate-differentiating cells, and its disruption decreased the CD11c promoter activity in a cell type-dependent manner. C/EBPalpha transactivated the CD11c promoter through the CEBP-80 element, and C/EBPalpha transactivation was also dependent on the Sp1-70- and Sp1-120 Sp1-binding sites. The -90/-50 fragment from the CD11c promoter, containing the adjacent CEBP-80, Sp1-70, and AP1-60 sites, differentially enhanced the activity of the minimal prolactin promoter in hematopoietic and epithelial cells. Altogether, these results demonstrate that C/EBP factors participate in the tissue-restricted and regulated expression of the CD11c/CD18 integrin through functional interactions with Sp1, suggest that Sp1-related factors modulate C/EBPalpha transcriptional activity on the CD11c promoter, and demonstrate the existence of a composite regulatory element recognized by C/EBP, Sp1, and AP-1 factors and whose enhancing effects are cell-type dependent.
López-Rodríguez
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Hospital de la Princesa, c/Diego de León 62, 28006 Madrid, Spain.
Botella
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Corbí
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D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D018845:CD11 Antigens / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D018845:CD11 Antigens; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors