Activation of Somatostatin Receptor II Expression by Transcription Factors MIBP1 and SEF-2 in the Murine Brain

Abstract

Somatostatin receptor type II expression in the mammalian brain displays a spatially and temporally very restricted pattern. In an investigation of the molecular mechanisms controlling these patterns, we have recently shown that 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 characterization of the promoter identified a species-conserved TC-rich enhancer 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 and 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 hybridization. While SEF-2 is widely expressed in many neuronal and nonneuronal tissues, MIBP1 expression overlapped precisely with expression of SSTR-2 in the frontal cortex and hippocampus. In summary, our data for the first time define a regulatory role for the transcription factor MIBP1 in mediating spatially and temporally regulated SSTR-2 expression in the brain.

ACKNOWLEDGMENTS

We are indebted to Kenshi Hayashi (Fukuoka, Japan) for providing the rat MIBP1 cDNA, to Richard B. Gaynor (University of Texas, Dallas) for providing the MIBP1/PRDII-BF1 zinc finger antiserum, to Pamela Mellon (San Diego, Calif.) for providing the cell line GHFT-1, and to Silvia Seegers for help with sequencing.

This work was supported by grants from the DFG to R.B. and R.S.

Equal contributions to this work were made by U.D. and A.P. Therefore, both should be considered first authors.