ZIC2 and Sp3 repress Sp1-induced activation of the human D1A dopamine receptor gene

Young Yang, Cheol Kyu Hwang, Eunsung Junn, Gwang Lee, M Maral Mouradian

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The human D1A dopamine receptor is transcribed from a tissue-specific regulated gene under the control of two promoters. An activator region (AR1) located between nucleotides -1154 and -1136 (relative to the first ATG) enhances transcription from the upstream promoter that is active in the brain. In this investigation, we sought to identify the nuclear factors that regulate the D1A gene through their binding to AR1 using yeast one-hybrid screening. Sp3 and Zic2 were among the positive clones isolated. Although Sp1 was not isolated from this screening and purified Sp1 alone does not bind to AR1 in gel shift experiments, this general transcription factor binds to AR1 in the presence of D1A expressing NS20Y nuclear extract and activates the D1A promoter. Thus, Sp1 appears to require an unknown factor(s) or post-translational modification to interact with AR1. On the other hand, Zic2 and Sp3 inhibit Sp1-induced activation of the D1A gene in an AR1-dependent manner. Zic2 and D1A genes have reciprocal brain regional distributions; Zic2 is expressed primarily in the cerebellum, and D1A is highly expressed in corpus striatum. These observations collectively suggest that one of the physiologic functions of Zic2 is repression of D1A gene transcription and that the intracellular balance among Sp1, Sp3 and Zic2 is important for regulating the tissue-specific expression of this dopamine receptor.

Original languageEnglish (US)
Pages (from-to)38863-38869
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number49
DOIs
StatePublished - Dec 8 2000

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Genes
Chemical activation
Transcription
General Transcription Factors
Brain
Screening
Corpus Striatum
Tissue
Dopamine Receptors
Post Translational Protein Processing
Cerebellum
Transcriptional Activation
Nucleotides
Clone Cells
Yeasts
Gels
Yeast
dopamine D1A receptor
Experiments

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "ZIC2 and Sp3 repress Sp1-induced activation of the human D1A dopamine receptor gene",
abstract = "The human D1A dopamine receptor is transcribed from a tissue-specific regulated gene under the control of two promoters. An activator region (AR1) located between nucleotides -1154 and -1136 (relative to the first ATG) enhances transcription from the upstream promoter that is active in the brain. In this investigation, we sought to identify the nuclear factors that regulate the D1A gene through their binding to AR1 using yeast one-hybrid screening. Sp3 and Zic2 were among the positive clones isolated. Although Sp1 was not isolated from this screening and purified Sp1 alone does not bind to AR1 in gel shift experiments, this general transcription factor binds to AR1 in the presence of D1A expressing NS20Y nuclear extract and activates the D1A promoter. Thus, Sp1 appears to require an unknown factor(s) or post-translational modification to interact with AR1. On the other hand, Zic2 and Sp3 inhibit Sp1-induced activation of the D1A gene in an AR1-dependent manner. Zic2 and D1A genes have reciprocal brain regional distributions; Zic2 is expressed primarily in the cerebellum, and D1A is highly expressed in corpus striatum. These observations collectively suggest that one of the physiologic functions of Zic2 is repression of D1A gene transcription and that the intracellular balance among Sp1, Sp3 and Zic2 is important for regulating the tissue-specific expression of this dopamine receptor.",
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ZIC2 and Sp3 repress Sp1-induced activation of the human D1A dopamine receptor gene. / Yang, Young; Hwang, Cheol Kyu; Junn, Eunsung; Lee, Gwang; Mouradian, M Maral.

In: Journal of Biological Chemistry, Vol. 275, No. 49, 08.12.2000, p. 38863-38869.

Research output: Contribution to journalArticle

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