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- Title
Human Act and AR1 Sequences Differentially Regulate Murine and Human D[sub14] Dopamine Receptor Promoters.
- Authors
Kim, Ok Soo; Kim, Hae Jung; Kwak, Hwan Jong; Lee, Jae-Hwa; Lee, Young Choon; Park, Mira; Kim, Mi Hyang; Lee, Gwang; Lee, Sang-Hyeon
- Abstract
The D[sub 14] dopamine rcecptor gene underlies complex transcriptional regulation in order to achieve the fixsue-specific expression. Transcription in the D[sub 14] genes proceeds from two distinct promoters utilized for the tissue-specific regulation of these genes. Furthermore, analysis of the human D[sub 1a] dopamine receptor gene has revealed that the region between nucleotides -1173 and -1136 (ActARI) of the gene might be important for its neural cell-specific expression. To investigate the function of D[sub 1a] dopamine receptor promoters in the brain cell-specific expression of transgenes. we analyzed the regulatory patterns of two distinct protein-binding regions of ActARI, i.e., an Act sequence (-1174/-1154) and an ARI sequence (-1154/-1136), toward murine and human D[sub 1a] promoters. Transient expression analyses using various chloramphenicol acetyltransferase constructs reveal that Act could not activate murine or human D[sub 14] promoters, and that ARI could effectively stimulate these promoters in a cell type-nonspecific manner. Only ActARI, a combination of Act and ARI, could activate murine and human D[sub 1a] prorooters in a prominent cell type-specific manner. Abundant protein binding to Act was detected by get mobility shift assay using nuclear extracts from SK-NS20Y, NS20Y, OK, and C6 but faint protein binding using nuclear extracts from HepG2. Furthermore, strong protein binding to AR1 was detected using nuclear extracts from SK-N-MC, NS20Y, HepG2 but faint protein binding from C6 extracts and no detectable protein binding from OK extracts. These observations suggest that the tissue-specific expression of the D[sub 14] gene is due, at least in part, to the differential expression of these activator proteins that bind to Act and ARI.
- Subjects
DOPAMINE; NEUROTRANSMITTERS; GENES; MOLECULAR genetics; PROTEINS
- Publication
Molecules & Cells (Springer Nature), 2003, Vol 15, Issue 3, p294
- ISSN
1016-8478
- Publication type
Article
- DOI
10.1016/s1016-8478(23)13740-x