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The transcription factors SP1 and MAZ regulate expression of the parathyroid hormone/parathyroid hormone-related peptide receptor gene.

Abstract
The parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor regulates extracellular calcium concentrations and is therefore important for mineral homeostasis. ROS 17/2.8 cells, a rat osteoblast-like osteosarcoma cell line, express the PTH/PTHrP receptor and provide a good model for examining the transcriptional regulation of its gene. The rat PTH/PTHrP receptor gene has two promoters, U1 and U3, which were shown to be important for its expression. Using extracts from ROS 17/2.8 cells, we have demonstrated two regions (termed FP1 and FP2) of nuclear protein/DNA interaction within promoter sequences previously shown to be important for the activity of the U3 promoter. Nuclear extracts from rat 2 fibroblasts, which do not express the PTH/PTHrP receptor, produced one site of protein/DNA interaction which was found at a position on the promoter identical to the position of FP1 produced by a ROS 17/2.8 nuclear extract. Mutation of these two sites of protein/DNA interaction resulted in reduced U3 promoter activity. Furthermore, we have demonstrated that the transcription factors SP1 and MAZ regulate U3 promoter expression and have shown their functional significance using mutational analysis. These data demonstrate that SP1 and MAZ bind to the PTH/PTHrP receptor promoter and that they are involved in cell-specific expression of its gene product.
AuthorsL J Williams, A B Abou-Samra
JournalJournal of molecular endocrinology (J Mol Endocrinol) Vol. 25 Issue 3 Pg. 309-19 (Dec 2000) ISSN: 0952-5041 [Print] England
PMID11116210 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Parathyroid Hormone
  • Sp1 Transcription Factor
  • Transcription Factors
  • c-MYC-associated zinc finger protein
  • DNA
Topics
  • Animals
  • Base Sequence (genetics)
  • DNA (physiology)
  • DNA-Binding Proteins
  • Electrophoresis
  • Fibroblasts (physiology)
  • Gene Expression Regulation (physiology)
  • Molecular Sequence Data
  • Mutation (physiology)
  • Nuclear Proteins (physiology)
  • Osteoblasts (physiology)
  • Promoter Regions, Genetic (physiology)
  • Rats
  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Parathyroid Hormone (genetics)
  • Sp1 Transcription Factor (physiology)
  • Transcription Factors (physiology)
  • Tumor Cells, Cultured

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