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GATA‐3 regulates the transcriptional activity of tyrosine hydroxylase by interacting with CREB
Author(s) -
Hong Seok Jong,
Huh Youngbuhm,
Chae Han,
Hong Sunghoi,
Lardaro Thomas,
Kim KwangSoo
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03924.x
Subject(s) - creb , transactivation , transcription factor , zinc finger , biology , tyrosine hydroxylase , neural crest , microbiology and biotechnology , gata transcription factor , creb binding protein , creb1 , promoter , transcription (linguistics) , gene , genetics , gene expression , neuroscience , dopamine , linguistics , philosophy
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.