AP-2 beta represses D-1A dopamine receptor gene transcription in Neuro2a cells

Takeuchi, Sousuke and Imafuku, Ichiro and Waragai, Masaaki and Roth, Christina and Kanazawa, Ichiro and Buettner, Reinhard and Mouradian, M. Maral and Okazawa, Hitoshi (1999) AP-2 beta represses D-1A dopamine receptor gene transcription in Neuro2a cells. MOLECULAR BRAIN RESEARCH, 74 (1-2). pp. 208-216. ISSN 0169-328X,

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Abstract

Expression of the D-1A dopamine receptor in brain is restricted to specific neuronal populations. To investigate the mechanism of this selective expression, we localized a silencer upstream of the human D-1A gene and identified its binding transcription factor in the D-1A-negative neural cell line Neuro2a. Using deletion CAT analysis, we narrowed this silencer to the region between nucleotides -561 and -532 relative to the CAP site. This 30-bp region, designated D1AS1, contains a sequence homologous to the AP-2 binding site and binds to a factor that also interacts with the AP-2 consensus sequence. In gel supershift assays, this factor is recognized by anti-AP-2 beta antibody. Co-transfection of Neuro2a cells with an AP-2 beta expression vector repressed the basal CAT activity of D-1A promoter-reporter plasmids in a D1AS1-dependent manner. RT-PCR analysis indicated that, among AP-2 family members, Neuro2a cells express only AP-2 beta. Furthermore, co-transfection of these cells with decoy oligonucleotides corresponding to the D1AS1 sequence de-repressed the D-1A gene promoter. Unlike in Neuro2a cells, AP-2 beta could not repress the D-1A promoter in the D-1A-positive neural cell line, NS20Y. in addition, the expression of AP-2 beta in different brain regions does not inversely correlate with that of D-1A dopamine receptor. These observations taken together indicate that AP-2 beta is a repressive transcription factor that acts on the D1AS1 silencer of the D-1A dopamine receptor gene via some cell-specific mechanism(s) in Neuro2a. (C) 1999 Elsevier Science B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: RETINOIC ACID; ENHANCER; IDENTIFICATION; EXPRESSION; CLONING; AP-2; DIFFERENTIATION; AP-2-ALPHA; PROTEIN; FAMILY; AP-2 beta; D-1A dopamine receptor; gene regulation; silencer; repressor; differentiation
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 06 Dec 2022 09:52
Last Modified: 06 Dec 2022 09:52
URI: https://pred.uni-regensburg.de/id/eprint/48770

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