A T-cell enhancer cooperates with NF-kappa B to yield cytokine induction of E-selectin gene transcription in endothelial cells

• Published in: The Journal of biological chemistry Vol. 267; no. 31; pp. 22385 - 22391
• Main Authors: Hooft van Huijsduijnen, R, Whelan, J, Pescini, R, Becker-André, M, Schenk, A M, DeLamarter, J F
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 05.11.1992
• Subjects: Base Sequence; Cell Adhesion Molecules - genetics; Cells, Cultured; Cytokines - pharmacology; DNA-Binding Proteins - metabolism; E-Selectin; Endothelium, Vascular - physiology; Enhancer Elements, Genetic; Gene Expression Regulation - drug effects; In Vitro Techniques; Molecular Sequence Data; NF-kappa B - physiology; Oligodeoxyribonucleotides - chemistry; Promoter Regions, Genetic; RNA, Messenger - genetics; T-Lymphocytes - physiology; Transcription, Genetic - drug effects
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)41683-3

ELAM1 (endothelial leukocyte adhesion molecule 1, also known as E-selectin) is a highly tissue-specific adhesion molecule that is transiently and exclusively expressed on cytokine-induced endothelial cells. We have identified two proximal ELAM1 promoter elements and their DNA-binding factors that are, in addition to NF-kappa B, essential for ELAM1 transcription. Mutation of either element in promoter constructs carrying the first 383 nucleotides of the ELAM1 promoter markedly diminshed the expression of a fused chloramphenicol acetyltransferase reporter gene. Although multimers of either element failed to display enhancer activity on its own, fusion of the most upstream of these to the NF-kappa B element had a strong stimulatory effect. This site, ACATCAT, is recognized by a factor we have called NF-ELAM1. The site corresponds to NF-ELAM1's preferential binding sequence (A/T)CA(G/T)CA(G/T) as determined in a target definition assay. This element is identical to the T-cell delta A enhancer found in the T-cell receptor-alpha, -beta, and CD3 delta genes. Our results suggest that the delta A/NF-ELAM1 element can function as a modulator of NF-kappa B in endothelial cells both as well as a T-cell enhancer.