Activation of somatostatin receptor II expression by transcription factors MIBP1 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 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.
Dörflinger
U
U
Institut für Experimentelle Krebsforschung, Klinik für Tumorbiologie an der Universität Freiburg, D-79106 Freiburg, Klinikum der RWTH Aachen, D-52074 Aachen, Germany.
Pscherer
A
A
Moser
M
M
Rümmele
P
P
Schüle
R
R
Buettner
R
R
D000595:Amino Acid Sequence; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D015723:Gene Library; D017930:Genes, Reporter / Q000235:genetics; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D051820:TCF Transcription Factors; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C490430:Hivep2 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; D051820:TCF Transcription Factors; C090743:Tcf4 protein, mouse; C491192:Tcf4 protein, rat; D000073940:Transcription Factor 4; D014157:Transcription Factors; C077171:HIVEP2 protein, human; C093733:somatostatin receptor 2