Abstract:
:Brn-4 is a member of the POU transcription factor family and is expressed in the central nervous system. In this study, we addressed whether Brn-4 regulates expression of the D1A dopamine receptor gene. We found a functional Brn-4 responsive element in the intron of this gene by means of cotransfection chloramphenical acetyltransferase assays. This region contains two consensus sequences for binding of POU factors. Gel mobility-shift assays using glutathione S-transferase-Brn-4 fusion protein indicated that Brn-4 binds to these sequences. Both these sites are essential for transactivation by Brn-4 because deletion of either significantly reduced this enhancer activity. In situ hybridization revealed colocalization of Brn-4 and D1A mRNAs at the level of a single neuron in the rat striatum where this dopamine receptor is most abundantly expressed. Gel mobility-supershift assay using rat striatal nuclear extract and Brn-4 antibody confirmed the presence of Brn-4 in this brain region and its ability to bind to its consensus sequences in the D1A gene. These data suggest a functional role for Brn-4 in the expression of the D1A dopamine receptor gene both in vitro and in vivo.
journal_name
Proc Natl Acad Sci U S Aauthors
Okazawa H,Imafuku I,Minowa MT,Kanazawa I,Hamada H,Mouradian MMdoi
10.1073/pnas.93.21.11933subject
Has Abstractpub_date
1996-10-15 00:00:00pages
11933-8issue
21eissn
0027-8424issn
1091-6490journal_volume
93pub_type
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