Polyomavirus enhancer-binding protein 2/core binding factor/acute myeloid leukemia factors contribute to the cell type-specific activity of the CD11a integrin gene promoter.
The CD11a/CD18 leukocyte integrin (LFA-1; also known as alphaL/beta2) mediates leukocyte transendothelial migration during immune and inflammatory responses and participates in lymphoma metastasis. CD11a/CD18 leukocyte-restricted expression is controlled by the CD11a gene promoter, which confers tissue-specific expression to reporter genes in vitro and in vivo. DNase I protection analysis of the CD11a proximal gene promoter revealed DNA-protein interactions centered at position -110 (CD11a-110). Disruption of CD11a-110 reduced CD11a promoter activity in a cell type-specific manner, as it reduced its activity by 70% in Jurkat lymphoid cells, whereas the effect was considerably lower in K562 and HepG2 cells. Electrophoretic mobility shift assays showed evidence of cell type-specific differences in CD11a-110 binding and indicated its specific recognition by members of the polyomavirus enhancer-binding protein 2/core binding factor (CBF)/acute myeloid leukemia (AML) family of transcription factors. AML1B/CBFbeta transactivated the CD11a promoter, with AML1B/CBFbeta-mediated transactivation being completely dependent on the integrity of the CD11a-110 element. Therefore, CBF/AML factors play a role in the cell type-restricted transcription of the CD11a integrin gene through recognition of CD11a-110. The involvement of CBF/AML factors in CD11a expression raises the possibility that CD11a/CD18 expression might be deregulated in acute myeloid and B-lineage acute lymphoblastic leukemias, thus contributing to their altered adhesion and metastatic potential.
Puig-Kröger
A
A
Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Cientificas, Madrid 28006, Spain.
López-Rodriguez
C
C
Relloso
M
M
Sánchez-Elsner
T
T
Nueda
A
A
Muñoz
E
E
Bernabéu
C
C
Corbi
A L
AL
D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation
D022762:CCAAT-Enhancer-Binding Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; D016169:Lymphocyte Function-Associated Antigen-1; D011518:Proto-Oncogene Proteins; C493728:RUNX1 protein, human; D050656:Transcription Factor AP-2; D014157:Transcription Factors