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(Received for publication, April 9, 1997, and in revised form, June 6, 1997)
From the Section of Plastic Surgery, Department of Surgery, Yale
University School of Medicine,
New Haven, Connecticut 06520-8041
Maximal gene expression driven by the promoter
for the transforming growth factor
Volume 272, Number 34,
Issue of August 22, 1997
pp. 21260-21267
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
Type I Receptor
type I receptor (TGF-RI)
occurs with a 1.0-kilobase pair fragment immediately upstream of exon
1. This region lacks a typical TATA box but contains CCAAT boxes,
multiple Sp1, and PEBP2/CBF
binding sites among other possible
cis-acting elements. Alterations within two CCAAT box
sequences do not mitigate reporter gene expression driven by the basal
promoter, and no nuclear factor binds to oligonucleotides encompassing
these sites. In contrast, other deletions or site-specific mutations
reveal an essential Sp1 site in the basal promoter and several
dispersed upstream Sp1 sites that contribute to maximal reporter gene
expression. The proportions of transcription factors Sp1 and Sp3, and
their ratios of binding to consensus elements, are maintained in bone cells at different stages of differentiation. Finally, nuclear factor
that binds to PEBP2/CBF-related cis-acting elements in the basal promoter sequence also occurs in osteoblasts. Our studies reveal that constitutive expression of TGF-RI may be determined by
constitutive nuclear factor binding to Sp1 sites, whereas other elements may account for the variations in TGF-RI levels that parallel changes in bone cell differentiation or activity.
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