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J. Cell Biol.,
Volume 140, Number 5, March 9, 1998 1265-1276
Department of Medicine and Department of Cell Biology, Washington University School of Medicine, St. Louis, Missouri 63110
Previously, we have suggested that vascular
cell adhesion molecule-1 (VCAM-1) and its integrin receptor 
4
1 mediate cell-cell interactions important
for skeletal myogenesis. Expression of the receptors
subsequently subsides in muscle after birth. Here, we
examine the mechanism regulating VCAM-1 gene expression in muscle. An enhancer located between the
TATA box and the transcriptional start site is responsible for VCAM-1 gene expression in muscle
this element is inactive in endothelial cells where VCAM-1 expression is dependent on nuclear factor 
B sites and
inflammatory cytokines. We identify interferon regulatory factor-2 (IRF-2), a member of the interferon regulatory factor family, as the enhancer-binding transcription factor and show that expression of IRF-2 parallels that of VCAM-1 during mouse skeletal myogenesis.
IRF-2 is not dependent upon cytokines for expression
or activity, and it has been shown to act as a repressor
in other nonmuscle cell types. We show that the basic
repressor motif located near the COOH-terminal of
IRF-2 is not active in muscle cells, but instead an acidic region in the center of the molecule functions as a
transactivating domain. Although IRF-2 and VCAM-1
expression diminishes on adult muscle fiber, they are
retained on myogenic stem cells (satellite cells). These
satellite cells proliferate and fuse to regenerate muscle
fiber after injury or disease. We present evidence that VCAM-1 on satellite cells mediates their interaction
with 41(+) leukocytes that invade the muscle after
injury or disease. We propose that VCAM-1 on endothelium generally recruits leukocytes to muscle after injury, whereas subsequent interaction with VCAM-1 on
regenerating muscle cells focuses the invading leukocytes specifically to the sites of regeneration.
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