The isolation and characterization of the promoter of the human type 1 inositol 1,4,5-trisphosphate receptor.
In humans, at least three types of inositol (1,4,5)-trisphosphate receptor (IP3R) are present. The gene encoding type 1 IP3R (IP3R-I) is expressed in all cell types, although expression predominates in Purkinje cells. To study the regulation of the human IP3R-I gene, we isolated and characterized a 2.1-kb 5' flanking region. In transient expression assays using a rat cell line, analysis of various deletion mutants demonstrated that a fragment of only 86 bp 5' of the putative tsp displayed a promoter activity similar to that of the 2.1-kb fragment. Also, we compared the sequence of the human IP3R-I promoter with the sequence of the mouse IP3R-I promoter. Considerable sequence homology is present in four distinct domains, which include several conserved putative binding sites for transcription factors. Further, we demonstrate a decrease in the activity of the isolated human IP3R-I promoter and of the endogenous IP3R-I promoter after 48 h of treatment with retinoic acid. Analysis of deletion constructs of the human promoter indicates that the decreased promoter activity in response to retinoic acid is likely to be mediated by a conserved AP-2 binding site.
Deelman
L E
LE
Department of Clinical Pharmacology, Groningen Institute for Drug Studies, University of Groningen, The Netherlands.
Jonk
L J
LJ
Henning
R H
RH
D000818:Animals; D001483:Base Sequence; D015220:Calcium Channels / Q000235:genetics*; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA; D005786:Gene Expression Regulation; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D004247:DNA