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 hepa rin, and mediates leukocyte adhesion, spreading, and migration, CD11c/ CD18 is primarily found on myeloid cells and its expression is regulat ed during myeloid differentiation by transcriptional mechanisms acting on the CD11c gene promoter, We now describe that CCAAT/enhancer-bindi ng proteins (C/EBP) contribute to the basal. tissue-specific and devel opmentally regulated activity of the CD11c promoter, A C/EBP-binding s ite within the CD11c promoter (CEBP-80) is bound by CEBP alpha in undi fferentiated U937 cells and by C/EBP alpha- and C/EBP beta-containing dimers in phorbol 12-myristate 13-acetate-differentiating cells, and i ts disruption decreased the CD11c promoter activity in a cell type-dep endent manner, C/EBP alpha transactivated the CD11c promoter through t he CEBP-80 element, and C/EBP alpha transactivation was also dependent on the Sp1-70- and Sp1-120 Spl binding sites. The -90/-50 fragment fr om the CD11c promoter, containing the adjacent CEBP-80, Sp1-70, and AP 1-60 sites, differentially enhanced the activity of the minimal prolac tin promoter in hematopoietic and epithelial cells, Altogether, these results demonstrate that C/EBP factors participate in the tissue-restr icted and regulated expression of the CD11c/CD18 integrin through func tional interactions with Sp1, suggest that Spl-related factors modulat e C/EBP alpha transcriptional activity on the CD11c promoter, and demo nstrate the existence of a composite regulatory element recognized by C/EBP, Spl, and AP-1 factors and whose enhancing effects are cell-type dependent.