Polyomavirus enhancer-binding protein 2/core binding factor/acute myeloid leukemia factors contribute to the cell type-specific activity of the CD11aintegrin gene promoter

The CD11a/CD18 leukocyte integrin (LFA-1; also known as alpha L/beta 2) med iates leukocyte transendothelial migration during immune and inflammatory r esponses and participates in lymphoma metastasis. CD11a/CD18 leukocyte-rest ricted expression is controlled by the CD11a gene promoter, which confers t issue-specific expression to reporter genes in vitro and in vivo. DNase I p rotection analysis of the CD11a proximal gene promoter revealed DNA-protein interactions centered at position -110 (CD11a-110). Disruption of CD11a-11 0 reduced CD11a promoter activity in a cell type-specific manner, as it red uced its activity by 70% in Jurkat lymphoid cells, whereas the effect was c onsiderably lower in K562 and HepG2 cells. Electrophoretic mobility shift a ssays showed evidence of cell type-specific differences in CD11a-110 bindin g and indicated its specific recognition by members of the polyomavirus enh ancer-binding protein 2/core binding factor (CBF)/acute myeloid leukemia (A ML) family of transcription factors. AML1B/CBF beta transactivated the CD11 a promoter, with AML1B/CBF beta-mediated transactivation being completely d ependent on the integrity of the CD11a-110 element. Therefore, CBF/AML fact ors play a role in the cell type-restricted transcription of the CD11a inte grin gene through recognition of CD11a-110, The involvement of CBF/AML fact ors in CD11a expression raises the possibility that CD11a/CD18 expression m ight be deregulated in acute myeloid and B-lineage acute lymphoblastic leuk emias, thus contributing to their altered adhesion and metastatic potential .