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Mol. Cell. Biol. doi:10.1128/MCB.01104-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

THE DROSOPHILA BHLH PROTEIN DIMMED DIRECTLY ACTIVATES PHM, A GENE ENCODING A NEUROPEPTIDE AMIDATING ENZYME

Department of Anatomy and Neurobiology, Department of Pediatrics, Washington University School of Medicine, 660 S. Euclid Ave. St. Louis, MO 63110; School of Biological Sciences, College of Natural Sciences, Seoul National University, 56-1 Shinlimdong Kwanakgu Seoul 151-742 Korea

^* To whom correspondence should be addressed. Email: taghertp{at}pcg.wustl.edu.

	Abstract

The basic helix-loop-helix (bHLH) protein DIMM supports the differentiation of secretory properties in numerous peptidergic cells of Drosophila. DIMM is co-expressed with diverse amidated neuropeptides, and with the amidating enzyme, peptidylglycine- -hydroxylating monooxygenase (PHM) in approximately 300 cells of the late embryo. Here we confirm that DIMM has transcription factor activity in transfected hEK-293 cells and that the PHM gene is a direct target. The mammalian DIMM-orthologue MIST1 also trans-activated the PHM gene. DIMM activity was dependent on the basic region of the protein and on the sequences of three E box sites within PHM's first intron; the sites make different contributions to the total activity. These data suggest a model whereby the three E boxes interact cooperatively and independently to produce high PHM transcriptional activation. This DIMM-controlled PHM regulatory region displayed similar properties in vivo. Spatially, its expression mirrored that of DIMM protein, and its activity was largely dependent on dimm. Further, in vivo expression was highly dependent on the sequences of the same three E boxes. This study supports the hypothesis that DIMM is a master regulator of a peptidergic cell fate in Drosophila and provides a detailed transcriptional mechanism of DIMM action on a defined target gene.