| First Author | Ohkawa N | Year | 1999 |
| Journal | Gene | Volume | 229 |
| Issue | 1-2 | Pages | 11-9 |
| PubMed ID | 10095099 | Mgi Jnum | J:53954 |
| Mgi Id | MGI:1333679 | Doi | 10.1016/s0378-1119(99)00048-7 |
| Citation | Ohkawa N, et al. (1999) Activation of the mouse inositol 1,4,5-trisphosphate receptor type 1 promoter by AP-2. Gene 229(1-2):11-9 |
| abstractText | Inositol 1,4,5-trisphosphate receptor (IP3R) functions as a Ca2+ channel that increases the intracellular Ca2+ upon binding to inositol trisphosphates. IP3R is expressed ubiquitously and consists of a multigene family. Since the type 1 IP3R (IP3R1) is highly expressed in the cerebellar Purkinje cells and moderately in hippocampus in the mammalian central nervous system (CNS), it is regarded as a neural member of this gene family. In this work, we investigated transcriptional regulation of the mouse ip3r1 gene. A DNaseI footprinting assay demonstrated that a sequence from -95 to -75, designated as box-II, was a binding site for a cerebellum-enriched factor. A consensus sequence for AP-2 was located in box-II. An electrophoretic mobility shift assay with anti-AP-2 antibody revealed that AP-2 is capable of binding to box-II. Deletion analysis of box-II showed that flanking sequences beside the box-II motif were required for the stable binding. We demonstrated by transient luciferase assay that exogenously expressed AP-2 activated box-II-dependent transcription. Moreover, we showed that endogenous AP-2 induced by retinoic acid also activated transcription via box-II in P19 cells. In-situ hybridization of the mouse brain revealed that AP-2 was predominantly expressed in the cerebellar Purkinje cells and hippocampal CA1 region, where IP3R1 is also highly expressed. From these observations, AP-2 binding to box-II is thought to be responsible for IP3R1 gene regulation in the CNS. |
