Transcription factor GATA-3 regulates the transcriptional activity of dopamine beta-hydroxylase by interacting with Sp1 and AP4.
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 beta-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.
Hong
Seok Jong
SJ
Molecular Neurobiology Laboratory, MRC215, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA, 02478, USA.
Choi
Hyun Jin
HJ
Hong
Sunghoi
S
Huh
Youngbuhm
Y
Chae
Han
H
Kim
Kwang-Soo
KS
D000818:Animals; D002478:Cells, Cultured; D004299:Dopamine beta-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011401:Promoter Regions, Genetic; D011784:Quail; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D050990:GATA3 Transcription Factor; D011993:Recombinant Fusion Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D004299:Dopamine beta-Hydroxylase