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Journal of Neuroscience, Vol 15, 8109-8120, Copyright © 1995 by Society for Neuroscience
A homeodomain protein selectively expressed in noradrenergic tissue regulates transcription of neurotransmitter biosynthetic genes
E Zellmer, Z Zhang, D Greco, J Rhodes, S Cassel and EJ Lewis
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201, USA.
In order to characterize the specificity of expression of the
neurotransmitter biosynthetic gene dopamine beta-hydroxylase (DBH), the
identification of proteins that interact with the DB1 enhancer was
initiated. A homeobox-containing cDNA was isolated from a PC12 expression
cDNA library screened with the DB1 enhancer. The homeodomain is a member of
the paired-like class, and is encoded by several nonidentical cDNAs. The
cDNAs contain the same sequence in the homeodomain and 3' coding and
noncoding sequences, but diverge in sequence 5' to the homeodomain. This
family of homeobox-containing cDNAs is named Arix. Arix mRNA transcripts
are found only in noradrenergic, DBH-positive tissues, and in cell lines
derived from those tissue. The DB1 enhancer contains two binding sites for
the Arix homeodomain, and both sites contribute to basal activity of the
DBH promoter. When introduced into tissue culture, Arix regulates the
transcriptional activity from the DBH promoter, and also from the promoter
of the tyrosine hydroxylase gene, encoding the initial enzyme of the
catecholamine biosynthetic pathway. The pattern of expression of the Arix
transcripts, the presence of the homeodomain, and the transcriptional
regulatory properties suggest that this family of proteins may be involved
in the specificity of expression of the catecholamine biosynthetic genes.
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