Gata-3 Regulates the Transcriptional Activity of Tyrosine Hydroxylase by Interacting with Creb.
From: Molecular Neurobiology Laboratory, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA.
Journal of neurochemistry
- Publish Date: Aug 2006
- ISSN: 0022-3042
- Volume: 98
- Issue: 3
- Pages: 773-81
- Medium: Print
- Language: English
- Citation (JAMA): Hong Seok Jong, Huh Youngbuhm, Chae Han, et al. Gata-3 Regulates the Transcriptional Activity of Tyrosine Hydroxylase by Interacting with Creb.. J. Neurochem. Aug 2006;98:773-81
Abstract
The zinc finger transcription factor GATA-3 is a master regulator of type 2 T-helper cell development. Interestingly, in GATA-3-/- mice, noradrenaline (NA) deficiency is a proximal cause of embryonic lethality. However, neither the role of GATA-3 nor its target gene(s) in the nervous system were known. Here, we report that forced expression of GATA-3 resulted in an increased number of tyrosine hydroxylase (TH) expressing neurons in primary neural crest stem cell (NCSC) culture. We also found that GATA-3 transactivates the promoter function of TH via specific upstream sequences, a domain of the TH promoter residing at -61 to -39 bp. Surprisingly, this domain does not contain GATA-3 binding sites but possesses a binding motif, a cAMP response element (CRE), for the transcription factor, CREB. In addition, we found that site-directed mutation of this CRE almost completely abolished transactivation of the TH promoter by GATA-3. Furthermore, protein-protein interaction assays showed that GATA-3 is able to physically interact with CREB in vitro as well as in vivo. Based on these results, we propose that GATA-3 may regulate TH gene transcription via a novel and distinct protein-protein interaction, and directly contributes to NA phenotype specification.
Mesh Headings (Keywords): Animals, Binding Sites, Cell Line, Tumor, Cells, Cultured, Chick Embryo, Coturnix, Cyclic AMP Response Element-Binding Protein, Enzyme Activation, GATA3 Transcription Factor, Gene Expression Regulation, Enzymologic, Hela Cells, Humans, Rats, Trans-Activation (Genetics), Tyrosine 3-Monooxygenase
Check for Full Text / PubMed Unique Identifier (PMID): 16893419
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