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Transcription Factor GATA-3 Regulates the Transcriptional Activity of Dopamine β-Hydroxylase by Interacting with Sp1 and AP4

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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.

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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).

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  1. Han Chae

    Present address: Pusan National University School of Oriental Medicine, 30 Jangjeon-Dong, Geumjeong-Gu, Busan, 609-735, Korea

Authors and Affiliations

  1. Molecular Neurobiology Laboratory, MRC215, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA

    Seok Jong Hong, Hyun Jin Choi, Sunghoi Hong, Youngbuhm Huh, Han Chae & Kwang-Soo Kim

  2. College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, 500-757, Korea

    Hyun Jin Choi

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  1. Seok Jong Hong
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Correspondence to Kwang-Soo Kim.

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Hong, S.J., Choi, H.J., Hong, S. et al. Transcription Factor GATA-3 Regulates the Transcriptional Activity of Dopamine β-Hydroxylase by Interacting with Sp1 and AP4. Neurochem Res 33, 1821–1831 (2008). https://doi.org/10.1007/s11064-008-9639-3

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