Transcription factor GATA-3 regulates the transcriptional activity of dopamine β-hydroxylase by interacting with Sp1 and AP4

Seok Jong Hong, Hyun Jin Choi, Sunghoi Hong, Youngbuhm Huh, Han Chae, Kwang Soo Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

GATA-3 is a zinc finger transcription factor that is expressed in T cell lineages as well as in the nervous system during development. In this study, we report that forced expression of GATA-3 resulted in an increased number of dopamine β-hydroxylase (DBH)-expressing neurons in primary neural crest stem cell (NCSC) culture, suggesting that the DBH gene may be a downstream target gene of GATA-3. GATA-3 robustly transactivates the promoter function of the noradrenaline (NA)-synthesizing DBH gene, via two specific upstream promoter domains; one at -62 to -32 bp and the other at -891 to -853 bp. Surprisingly, none of these domains contain GATA-3 binding sites but encompass binding motifs for transcription factors Sp1 and AP4, respectively. Protein-protein interaction analyses both in vitro and in vivo and chromatin immunoprecipitation (ChIP) assays showed that GATA-3 effects its transcriptional regulatory function through physical interactions with these transcription factors.

Original languageEnglish (US)
Pages (from-to)1821-1831
Number of pages11
JournalNeurochemical Research
Volume33
Issue number9
DOIs
StatePublished - Sep 2008

Funding

Acknowledgements The authors thank J. Engel for chick GATA-3 clone, R. Ratan for the Sp1 expressing plasmids, C. Tabin for RCASBP vectors and pSlax13, and O. Andrisani for NCSC culture. This work was supported by NIH grants (MH48866 and DC006501).

Keywords

  • AP4
  • ChIP assay
  • Dopamine β-hydroxylase
  • GATA-3
  • Protein-protein interaction
  • Sp1
  • siRNA

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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