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. 1994 Nov 22;91(24):11641–11645. doi: 10.1073/pnas.91.24.11641

Regulatory elements and transcription factors controlling basal and cytokine-induced expression of the gene encoding intercellular adhesion molecule 1.

J Hou 1, V Baichwal 1, Z Cao 1
PMCID: PMC45287  PMID: 7972116

Abstract

The gene encoding intercellular adhesion molecule 1 (ICAM-1) is transcriptionally induced in response to inflammatory and immunomodulatory cytokines. To investigate the mechanisms controlling ICAM-1 gene expression, we have identified regulatory DNA sequences responsible for maintaining basal and mediating induced transcription in response to tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). Regulatory elements centered 115, 60, and 40 bp upstream from the ICAM-1 transcription start site were implicated in cytokine-independent gene expression. Regulatory elements dedicated to TNF-alpha and IFN-gamma were identified 190 and 90 bp, respectively, upstream from the ICAM-1 transcription start site. A combination of mutagenesis and DNA-binding assays revealed that the TNF-alpha response element is composite, consisting of binding sites for both C/EBP and NF-kappa B. The IFN-gamma response element behaved as a simple regulatory element that selectively binds to an IFN-gamma-inducible activity composed, at least in part, of p91. These observations provide a framework for understanding how extracellular signals dynamically regulate the adhesive properties of mammalian cells.

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