Transcriptional regulation of mouse type 1 inositol 1,4,5-trisphosphate receptor gene by NeuroD-related factor

The type 1 inositol 1,4,5-trisphosphate receptor (IP(3)R1) is a Ca2+ channe l protein that is expressed abundantly in the CNS, such as in the cerebella r Purkinje cells and hippocampus. We previously demonstrated that the box-1 element, which is located -334 relative to the transcription initiation si te of the mouse IP(3)R1 gene and includes an E-box consensus sequence, is i nvolved in the up-regulation of such IP,RI gene expression. Furthermore, th e previous study also indicated that some CNS-related basic helix-loop-heli x (bHLH) factors bind to the box-1 and activate IP(3)R1 gene expression. in this study, we demonstrated that one of the CNS-related bHLH factors, neur onal differentiation factor (NeuroD)related factor (NDRF), specifically bou nd to the box-1 sequence with a ubiquitously expressed bHLH protein, E47, a nd activated IP(3)R1 gene expression. In situ hybridization of adult mouse brain revealed that IP(3)R1 and NDRF mRNA were cc-expressed in many subsets of neurons, highly in Purkinje cells and hippocampus and moderately in cer ebral cortex, olfactory bulb, and caudate putamen. Furthermore, the spatiot emporal expression patterns of these two genes resembled one another throug hout postnatal development of the mouse CNS. From these results, we suggest that NDRF is involved in the tissue-specific regulation of IP(3)R1 gene ex pression in the CNS.