Open AccessRegulatory elements and transcription factors controlling basal and cytokine-induced expression of the gene encoding intercellular adhesion molecule 1.
Author(s) -
Jinzhao Hou,
Vijay Baichwal,
Zhaodan Cao
Publication year - 1994
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.91.24.11641
Subject(s) - biology , transcription factor , response element , gene expression , microbiology and biotechnology , transcription (linguistics) , intercellular adhesion molecule 1 , gene , regulation of gene expression , regulatory sequence , promoter , cytokine , nfkb1 , cell adhesion molecule , genetics , linguistics , philosophy
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.