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 rece ptor (IP3R) are present. The gene encoding type 1 IP3R (IP3R-I) is exp ressed 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 de monstrated that a fragment of only 86 bp 5' of the putative tsp displa yed a promoter activity similar to that of the 2.1-kb fragment. Also, we compared the sequence of the human IP3R-T promoter with the sequenc e of the mouse IP3R-I promoter. Considerable sequence homology is pres ent in four distinct domains, which include several conserved putative binding sites for transcription factors. Further, we demonstrate a de crease in the activity of the isolated human IP3R-I promoter and of th e endogenous IP3R-I promoter after 48 h of treatment with retinoic aci d. Analysis of deletion constructs of the human promoter indicates tha t the decreased promoter activity in response to retinoic acid is like ly to be mediated by a conserved AP-2 binding site. (C) 1998 Elsevier Science B.V.