Transcriptional regulation of endothelial cell adhesion molecules: NF‐κB and cytokine‐inducible enhancers

T Collins, MA Read, AS Neish, MZ Whitley… - The FASEB …, 1995 - Wiley Online Library
T Collins, MA Read, AS Neish, MZ Whitley, D Thanos, T Maniatis
The FASEB Journal, 1995Wiley Online Library
Transcription of endothelial‐leukocyte adhesion molecule‐1 (E‐selectin or ELAM‐1),
vascular cell adhesion molecule‐1 (VCAM‐1), and intercellular adhesion molecule‐l (ICAM‐
1) is induced by the inflammatory cytokines interleukin‐1 β (IL‐lβ) and tumor necrosis faetor‐
α (TNFα). The positive regulatory domains required for maximal levels of cytokine induction
have been defined in the promoters of all three genes. DNA binding studies reveal a
requirement for nuclear factor‐κB (NF‐κB) and a small group of other transcriptional …
Transcription of endothelial‐leukocyte adhesion molecule‐1 (E‐selectin or ELAM‐1), vascular cell adhesion molecule‐1 (VCAM‐1), and intercellular adhesion molecule‐l (ICAM‐1) is induced by the inflammatory cytokines interleukin‐1 β (IL‐lβ) and tumor necrosis faetor‐α (TNFα). The positive regulatory domains required for maximal levels of cytokine induction have been defined in the promoters of all three genes. DNA binding studies reveal a requirement for nuclear factor‐κB (NF‐κB) and a small group of other transcriptional activators. The organization of the cytokine‐inducible element in the E‐se‐ lectin promoter is remarkably similar to that of the virus‐indueible promoter of the human interferon‐β gene in that both promoters require NF‐κB, activating transcription factor‐2 (ATF‐2), and high mobility group protein I(Y) for induction. Based on this structural similarity, a model has been proposed for the cytokine‐induced E‐selectin enhancer that is similar to the stereospecific complex proposed for the inter‐ feron‐β gene promoter. In these models, multiple DNA bending proteins facilitate the assembly of higher order complexes of transcriptional activators that interact as a unit with the basal transcriptional machinery. The assembly of unique enhancer complexes from similar sets of transcriptional factors may provide the specificity required to regulate complex patterns of gene expression and correlate with the distinct patterns of expression of the leukocyte adhe‐sion molecules.—Collins, T., Read, M. A., Neisli, A. S., Whitley, M. Z., Thanos, D., Maniatis, T. Transcriptional regulation of endothelial cell adhesion molecules: NF‐κB and cytokine‐indueible enhancers. FASEBJ. 9, 899‐909 (1995)
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