TY - JOUR
T1 - 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
AU - Selvamurugan, Nagarajan
AU - Chou, Wan Yin
AU - Pearman, A. Terrece
AU - Pulumati, Malini R.
AU - Partridge, Nicola C.
PY - 1998/4/24
Y1 - 1998/4/24
N2 - Parathyroid hormone induces collagenase-3 gene transcription in rat osteoblastie 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 -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-β 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.
AB - Parathyroid hormone induces collagenase-3 gene transcription in rat osteoblastie 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 -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-β 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.
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U2 - 10.1074/jbc.273.17.10647
DO - 10.1074/jbc.273.17.10647
M3 - Article
C2 - 9553127
AN - SCOPUS:0032562581
SN - 0021-9258
VL - 273
SP - 10647
EP - 10657
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 17
ER -