A T-cell enhancer cooperates with NF-kappa B to yield cytokine induction of E-selectin gene transcription in endothelial cells.
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.
Hooft van Huijsduijnen
R
R
Glaxo Institute for Molecular Biology, Chemin des Aulx, Geneva, Switzerland.
Whelan
J
J
Pescini
R
R
Becker-André
M
M
Schenk
A M
AM
DeLamarter
J F
JF
D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D013601:T-Lymphocytes / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D015815:Cell Adhesion Molecules; D016207:Cytokines; D004268:DNA-Binding Proteins; D019040:E-Selectin; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger