A striking similarity in the organization of the E-selectin and beta interferon gene promoters
| Autor: | Tucker Collins, T Maniatis, Margaret A. Read, Maryann Z. Whitley, Dimitris Thanos |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Oncogene Proteins v-rel
Transcription Genetic Recombinant Fusion Proteins DNA Mutational Analysis Molecular Sequence Data Retroviridae Proteins Oncogenic Transcription (biology) Gene expression Humans HMGA1a Protein Binding site Cyclic AMP Response Element-Binding Protein Promoter Regions Genetic Gene Transcription factor Molecular Biology Cells Cultured Regulation of gene expression biology Activating Transcription Factor 2 Base Sequence Models Genetic High Mobility Group Proteins NF-kappa B Promoter Interferon-beta Cell Biology Molecular biology Activating transcription factor 2 Gene Expression Regulation Growth Hormone biology.protein Cytokines Endothelium Vascular E-Selectin Cell Adhesion Molecules Research Article Protein Binding Transcription Factors |
| Zdroj: | Molecular and Cellular Biology. 14:6464-6475 |
| ISSN: | 1098-5549 0270-7306 |
| DOI: | 10.1128/mcb.14.10.6464 |
| Popis: | Transcription of the endothelial leukocyte adhesion molecule 1 (E-selectin or ELAM-1) gene is induced by the inflammatory cytokines interleukin-1 beta and tumor necrosis factor alpha (TNF-alpha). In this report, we identify four positive regulatory domains (PDI to PDIV) in the E-selectin promoter that are required for maximal levels of TNF-alpha induction in endothelial cells. In vitro DNA binding studies reveal that two of the domains contain novel adjacent binding sites for the transcription factor NF-kappa B (PDIII and PDIV), a third corresponds to a recently described CRE/ATF site (PDII), and a fourth is a consensus NF-kappa B site (PDI). Mutations that decrease the binding of NF-kappa B to any one of the NF-kappa B binding sites in vitro abolished cytokine-induced E-selectin gene expression in vivo. Previous studies demonstrated a similar correlation between ATF binding to PDII and E-selectin gene expression. Here we show that the high-mobility-group protein I(Y) [HMG I(Y)] also binds specifically to the E-selectin promoter and thereby enhances the binding of both ATF-2 and NF-kappa B to the E-selectin promoter in vitro. Moreover, mutations that interfere with HMG I(Y) binding decrease the level of cytokine-induced E-selectin expression. The organization of the TNF-alpha-inducible element of the E-selectin promoter is remarkably similar to that of the virus-inducible promoter of the human beta interferon gene in that both promoters require NF-kappa B, ATF-2, and HMG I(Y). We propose that HMG I(Y) functions as a key architectural component in the assembly of inducible transcription activation complexes on both promoters. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|