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 language | English (US) |
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Pages (from-to) | 1821-1831 |
Number of pages | 11 |
Journal | Neurochemical Research |
Volume | 33 |
Issue number | 9 |
DOIs | |
State | Published - 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