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J Biol Chem, Vol. 273, Issue 17, 10647-10657, April 24, 1998
From the Department of Pharmacological and Physiological Science,
Saint Louis University School of Medicine, St.
Louis, Missouri 63104
Parathyroid hormone induces collagenase-3
gene transcription in rat osteoblastic cells. Here, we characterized
the basal, parathyroid hormone regulatory regions of the rat
collagenase-3 gene and the proteins involved in this regulation. The
minimal parathyroid hormone-responsive region was observed to be
between base pairs
Parathyroid Hormone Regulates the Rat Collagenase-3 Promoter
in Osteoblastic Cells through the Cooperative Interaction of the
Activator Protein-1 Site and the runt Domain Binding
Sequence
38 and 148. Deleted and mutated constructs
showed that the activator protein-1 and the runt domain
binding sites are both required for basal expression and parathyroid
hormone activation of this gene. The runt domain site is
identical to an osteoblast-specific element-2 or acute myelogenous
leukemia binding sequence in the mouse and rat osteocalcin genes,
respectively. Overexpression of an acute myelogenous leukemia-1
repressor protein inhibited parathyroid hormone activation of the
promoter, indicating a requirement of acute myelogenous
leukemia-related factor(s) for this activity. Overexpression of c-Fos,
c-Jun, osteoblast-specific factor-2, and core binding factor-
increased the response to parathyroid hormone of the wild type (148)
promoter but not with mutation of either or both the activator
protein-1 and runt domain binding sites. In summary, we
conclude that there is a cooperative interaction of acute myelogenous
leukemia/polyomavirus enhancer-binding protein-2-related factor(s)
binding to the runt domain binding site with members of the
activator protein-1 transcription factor family binding to the
activator protein-1 site in the rat collagenase-3 gene in response to
parathyroid hormone in osteoblastic cells.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
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