Cloning and characterization of the type I inositol 1,4,5-trisphosphate receptor gene promoter. Regulation by 17beta-estradiol in osteoblasts

J Biol Chem. 1997 Sep 5;272(36):22425-31. doi: 10.1074/jbc.272.36.22425.

Abstract

The inositol 1,4,5-trisphosphate (InsP3) receptor is essential for signal Ca2+ release from intracellular stores and for capacitative Ca2+ entry. We have isolated the promoter and proximal DNA segments of the human type I InsP3 receptor gene. Transcription initiation in human G-292 osteosarcoma and HL-60 promyelocytic leukemia cells was shown to occur predominantly from an adenine residue located 39 base pairs downstream of a consensus TATA box element. Upstream DNA including the TATA box promoted directional transcription of a chloramphenicol acetyltransferase reporter gene when transfected into G-292 cells. A negative regulatory element in the distal promoter and a positive element in the proximal region were identified by deletion mapping and transcription assays. The proximal region enhanced transcription in response to 12-O-tetradecanoylphorbol-13-acetate or serum, but conferred transcriptional repression in response to 1,25-dihydroxyvitamin D3 or 17beta-estradiol. The repressive effect of 17beta-estradiol was mediated by the nuclear estrogen receptor, as estrogen-dependent transcriptional repression was inhibited by the antiestrogen tamoxifen and the estrogen receptor antagonist ICI 182,780. This is the first study of the type I InsP3 receptor gene promoter, and the results suggest a mechanism by which chronic estrogen treatment of osteoblasts affects type I InsP3 receptor gene expression, signal transduction, and secretion.

MeSH terms

  • Base Sequence
  • Calcium Channels / genetics*
  • Calcium Channels / metabolism
  • Cloning, Molecular
  • Estradiol / analogs & derivatives
  • Estradiol / pharmacology*
  • Estrogen Antagonists / pharmacology
  • Fulvestrant
  • Gene Expression Regulation / drug effects*
  • Humans
  • Inositol 1,4,5-Trisphosphate / metabolism*
  • Inositol 1,4,5-Trisphosphate Receptors
  • Molecular Sequence Data
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Promoter Regions, Genetic*
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Tamoxifen / pharmacology
  • Transcription, Genetic
  • Tumor Cells, Cultured

Substances

  • Calcium Channels
  • Estrogen Antagonists
  • ITPR1 protein, human
  • Inositol 1,4,5-Trisphosphate Receptors
  • Receptors, Cytoplasmic and Nuclear
  • Tamoxifen
  • Fulvestrant
  • Estradiol
  • Inositol 1,4,5-Trisphosphate

Associated data

  • GENBANK/AF009963