GATA-3 regulates the transcriptional activity of tyrosine hydroxylase by interacting with CREB

Jong Hong Seok, Youngbuhm Huh, Han Chae, Sunghoi Hong, Thomas Lardaro, Kwang Soo Kim

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The zinc finger transcription factor GATA-3 is a master regulator of type 2T-helper cell development. Interestingly, in GATA-3-/-mice, noradrenaline (NA) deficiency is a proximal cause of embryonic lethality. However, neitherthe 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.

Original languageEnglish
Pages (from-to)773-781
Number of pages9
JournalJournal of Neurochemistry
Volume98
Issue number3
DOIs
Publication statusPublished - 2006 Aug 1
Externally publishedYes

Fingerprint

Tyrosine 3-Monooxygenase
Response Elements
GATA3 Transcription Factor
Norepinephrine
Proteins
Genes
Transcription Factor 3
GATA Transcription Factors
Neural Stem Cells
Neural Crest
Zinc Fingers
Neurology
Transcription
Helper-Inducer T-Lymphocytes
Stem cells
Cell culture
Nervous System
Transcriptional Activation
Neurons
Zinc

Keywords

  • Neural crest stem cells
  • Protein-protein interaction
  • Sympathetic neuron
  • Transcription factors
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

GATA-3 regulates the transcriptional activity of tyrosine hydroxylase by interacting with CREB. / Seok, Jong Hong; Huh, Youngbuhm; Chae, Han; Hong, Sunghoi; Lardaro, Thomas; Kim, Kwang Soo.

In: Journal of Neurochemistry, Vol. 98, No. 3, 01.08.2006, p. 773-781.

Research output: Contribution to journalArticle

Seok, Jong Hong ; Huh, Youngbuhm ; Chae, Han ; Hong, Sunghoi ; Lardaro, Thomas ; Kim, Kwang Soo. / GATA-3 regulates the transcriptional activity of tyrosine hydroxylase by interacting with CREB. In: Journal of Neurochemistry. 2006 ; Vol. 98, No. 3. pp. 773-781.
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