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 CEBPα in undifferentiated U937 cells and by C/EBPα- and C/EBPβ-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/EBPα transactivated the CD11c promoter through the CEBP-80 element, and C/EBPα 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/EBPα 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.

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