Journal Article

Vascular Cell Adhesion Molecule 1: Contrasting Transcriptional Control Mechanisms in Muscle and Endothelium

Iademarco, Michael F., Dean, Douglas C., McQuillan, Jay J.

1993

Overview

Interaction between vascular cell adhesion molecule 1 (VCAM-1), which appears on the surface of endothelial cells in response to inflammation, and its integrin counter receptor, α 4β 1, on immune cells is responsible for targeting these immune cells to cytokine-stimulated endothelium. In addition to its role in the immune system, VCAM-1 is also expressed in a developmentally specific pattern on differentiating skeletal muscle, where it mediates cell-cell interactions important for myogenesis through interaction with α 4β 1. In contrast to endothelium, there is high basal expression of VCAM-1 in skeletal muscle cells and the expression is not cytokine-responsive. Here, we examine the molecular basis for these contrasting patterns of expression in muscle and endothelium, using VCAM-1 promoter constructs in a series of transfection assays. In endothelial cells, octamer binding sites act as silencers that prevent VCAM-1 expression in unstimulated cells. Tumor necrosis factor α overcomes the negative effects of these octamers and activates the promoter through two adjacent NF-κ B binding sites. In muscle cells, a position-specific enhancer located between bp -21 and -5 overrides the effect of other promoter elements, resulting in constitutive VCAM-1 expression. A nuclear protein binds the position-specific enhancer in muscle but not endothelial cells; thus the pattern of expression of this protein could control enhancer activity.

• Publisher: National Academy of Sciences of the United States of America,National Acad Sciences,National Academy of Sciences
• Subject: Adhesion / Animals / B lymphocytes / Base Sequence / Biochemistry / Biological and medical sciences / Cell Adhesion Molecules - biosynthesis / Cell Adhesion Molecules - genetics / Cell Line / Cell lines / Cells / Cells, Cultured / Cellular differentiation / Chloramphenicol O-Acetyltransferase - genetics / Chloramphenicol O-Acetyltransferase - metabolism / Endothelial cells / Endothelium, Vascular - metabolism / Fundamental and applied biological sciences. Psychology / Gene expression / Gene Expression Regulation / Genetic mutation / Human umbilical vein endothelial cells / Humans / Immunity (Disease) / Molecular and cellular biology / Molecular genetics / Molecular Sequence Data / Muscles - metabolism / Muscular system / NF-kappa B - metabolism / Oligodeoxyribonucleotides / Organ Specificity / Plasmids / Promoter regions / Promoter Regions, Genetic / Restriction Mapping / Silencers / T lymphocytes / TATA Box / Transcription, Genetic / Transfection / Tumor Cells, Cultured / Umbilical Veins / Vascular Cell Adhesion Molecule-1