| First Author | Kirkwood KL | Year | 1997 |
| Journal | J Biol Chem | Volume | 272 |
| Issue | 36 | Pages | 22425-31 |
| PubMed ID | 9278393 | Mgi Jnum | J:42744 |
| Mgi Id | MGI:1096229 | Doi | 10.1074/jbc.272.36.22425 |
| Citation | Kirkwood KL, et al. (1997) Cloning and characterization of the type I inositol 1,4,5-trisphosphate receptor gene promoter. Regulation by 17beta-estradiol in osteoblasts. J Biol Chem 272(36):22425-31 |
| abstractText | 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. |
