Cloning and characterization of the 5'-transcriptional regulatory region of the human intercellular adhesion molecule 1 gene

• Published in: The Journal of biological chemistry Vol. 266; no. 21; pp. 14024 - 14030
• Main Authors: DEGITZ, K, LI LIAN-JIE, WRIGHT CAUGHMAN, S
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25.07.1991
• Subjects: Amino Acid Sequence; Base Sequence; Biological and medical sciences; Cell Adhesion Molecules - genetics; Cloning, Molecular; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genes; Humans; Intercellular Adhesion Molecule-1; Interferon-gamma - pharmacology; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Oligonucleotides - chemistry; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; Repressor Proteins - physiology; Restriction Mapping; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Human; Regulation(control); Gene; Transcription; Transcription promoter; Cell adhesion molecule; Restriction map; Molecular cloning
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)92805-x

Cell-cell adhesion is critical in the generation of immunologic responses and is dependent upon expression of a variety of cell surface receptors. While intercellular adhesion molecule 1 (ICAM-1), a specific receptor for lymphocyte function-associated antigen 1, is constitutively expressed by some cell types, its de novo or increased expression by various cells has been associated with the initiation of inflammatory responses and appears to be transcriptionally regulated. The 5' region of the human ICAM-1 gene has been cloned and both structurally and functionally analyzed. A 17.3-kilobase genomic clone containing three exonal regions encoding the N-terminal third of the ICAM-1 protein was isolated. A 2.05-kilobase subclone, containing the 5' most exon, was utilized to determine an interferon-gamma-induced transcription initiation site via primer extension and S1 nuclease protection assays. Analysis of the 5'-flanking region revealed consensus sequences for appropriately located basal promoter elements, as well as numerous potential cis-acting enhancer elements. When subcloned into a reporter gene construct, the putative promoter subregion functioned as a potent promoter. However, in accord with biologically observed expression of ICAM-1 in specific cell types, when additional 5'-flanking sequences were included in reporter gene constructs, tissue appropriate repression of transcription was observed.