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Identification of Sp1‐binding sites in the CD11c (p150,95α) and CD11a (LFA‐1α) integrin subunit promoters and their involvement in the tissuespecific expression of CD11c
Author(s) -
LópezRodríguez Cristina,
Chen HuiMin,
Tenen Daniel G.,
Corbí Angel L.
Publication year - 1995
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830251243
Subject(s) - biology , integrin , cd11c , identification (biology) , promoter , protein subunit , cd11a , expression (computer science) , microbiology and biotechnology , integrin alpha m , cd18 , genetics , phenotype , gene expression , receptor , botany , gene , computer science , flow cytometry , programming language
Abstract The leukocyte integrins LFA‐1 (CD11a/CD18) and p150,95 (CD11c/CD18) mediate cell‐cell and cell‐extracellular matrix interactions during inflammatory responses and signal transduction into the cytoplasm. While the CD11a integrin subunit is expressed on all leukocytes, CD11c is almost exclusively expressed on cells of the myeloid lineage and on activated B lymphocytes. Its expression is regulated during cell activation and differentiation by transcriptional mechanisms. We have previously demonstrated that the proximal region of the CD11c promoter directs tissue‐restricted and developmentally‐regulated expression of reporter genes. Structural studies by electrophoretic mobility shift assays have demonstrated the presence of two Sp1‐binding sites at −70 (Sp1–70) and−120 (Sp1–120) which mediate the Sp1 transactivation of the CD11c promoter in Sp1‐defective SL2 cells, and which are involved in cell lineage‐specific DNA‐protein interactions, as demonstrated by footprinting in vivo . More importantly, mutation of either Sp1 site inhibited the activity of the CD11c promoter both in myeloid U937 cells and the CD11c‐expressing B lymphoblastoid JY cell line, while the opposite effect was observed in the CD11c‐negative epithelial HeLa cell line, demonstrating the involvement of both Sp1‐binding sites in the basal and the tissue‐restricted expression of the CD11c integrin subunit gene. Interestingly, the analysis of the CD11a proximal promoter also revealed the existence of an Sp1‐binding site at−70, indicating a common role for these cis ‐acting elements in the transcription of the leukocyte integrin α subunit genes. The binding of Sp1 to the regulatory regions of the leukocyte integrin genes raises the possibility that the retinoblastoma susceptibility gene product is implicated in integrin expression through its functional interaction with Sp1, thus establishing a link between integrin‐dependent leukocyte adhesiveness and the state of cellular differentiation/proliferation.