期刊
JOURNAL OF NEUROCHEMISTRY
卷 98, 期 3, 页码 773-781出版社
BLACKWELL PUBLISHING
DOI: 10.1111/j.1471-4159.2006.03924.x
关键词
neural crest stem cells; protein-protein interaction; sympathetic neuron; transcription factors; tyrosine hydroxylase
资金
- NIDCD NIH HHS [DC006501] Funding Source: Medline
- NIMH NIH HHS [MH48866] Funding Source: Medline
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.
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