Activation of somatostatin receptor II expression by transcription factorsMIBP1 and SEF-2 in the murine brain

Somatostatin receptor type II expression in the mammalian brain displays a spatially and temporally very restricted pattern. In an investigation of th e molecular mechanisms controlling these patterns, we have recently shown t hat binding of the transcription factor SEF-2 to a novel initiator element in the SSTR-2 promoter is essential for SSTR-2 gene expression. Further cha racterization of the promoter identified a species-conserved TC-rich enhanc er element. By screening a mouse brain cDNA expression library, we cloned a cDNA encoding the transcription factor MIBP1. MIBP1 interacts specifically with both the TC box in the SSTR-2 promoter arid with the SEF-2 initiator- binding protein to enhance transcription from the basal SSTR-2 promoter. We then investigated SSTR-2, SEF-2, and MIBP1 mRNA expression patterns in the developing and adult murine brain by Northern blotting and in situ hybridi zation. While SEF-2 is widely expressed in many neuronal and nonneuronal ti ssues, MIBP1 expression overlapped precisely with expression of SSTR-2 in t he frontal cortex and hippocampus. In summary, our data for the first time define a regulatory role for the transcription factor MIBP1 in mediating sp atially and temporally regulated SSTR-2 expression in the brain.